Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease
Publication: Antioxidants & Redox Signaling
Volume 31, Issue Number 12
Abstract
Significance: Oxidative stress in the cell is characterized by excessive generation of reactive oxygen species (ROS). Superoxide (O2−) and hydrogen peroxide (H2O2) are the main ROS involved in the regulation of cellular metabolism. As our fundamental understanding of the underlying causes of lung disease has increased it has become evident that oxidative stress plays a critical role.
Recent Advances: A number of cells in the lung both produce, and respond to, ROS. These include vascular endothelial and smooth muscle cells, fibroblasts, and epithelial cells as well as the cells involved in the inflammatory response, including macrophages, neutrophils, eosinophils. The redox system is involved in multiple aspects of cell metabolism and cell homeostasis.
Critical Issues: Dysregulation of the cellular redox system has consequential effects on cell signaling pathways that are intimately involved in disease progression. The lung is exposed to biomechanical forces (fluid shear stress, cyclic stretch, and pressure) due to the passage of blood through the pulmonary vessels and the distension of the lungs during the breathing cycle. Cells within the lung respond to these forces by activating signal transduction pathways that alter their redox state with both physiologic and pathologic consequences.
Future Directions: Here, we will discuss the intimate relationship between biomechanical forces and redox signaling and its role in the development of pulmonary disease. An understanding of the molecular mechanisms induced by biomechanical forces in the pulmonary vasculature is necessary for the development of new therapeutic strategies.
Get full access to this article
View all available purchase options and get full access to this article.
References
1. Adatia I, Kothari SS, and Feinstein JA. Pulmonary hypertension associated with congenital heart disease: pulmonary vascular disease: the global perspective. Chest 137: 52S–61S, 2010.
2. Agbani EO, Coats P, Mills A, and Wadsworth RM. Peroxynitrite stimulates pulmonary artery endothelial and smooth muscle cell proliferation: involvement of ERK and PKC. Pulm Pharmacol Ther 24: 100–109, 2011.
3. Aggarwal S, Gross CM, Kumar S, Dimitropoulou C, Sharma S, Gorshkov BA, Sridhar S, Lu Q, Bogatcheva NV, Jezierska-Drutel AJ, Lucas R, Verin AD, Catravas JD, and Black SM. Dimethylarginine dimethylaminohydrolase II overexpression attenuates LPS-mediated lung leak in acute lung injury. Am J Respir Cell Mol Biol 50: 614–625, 2014.
4. Aggarwal S, Gross CM, Sharma S, Fineman JR, and Black SM. Reactive oxygen species in pulmonary vascular remodeling. Compr Physiol 3: 1011–1034, 2013.
5. Altenhöfer S, Radermacher KA, Kleikers PW, Wingler K, and Schmidt HH. Evolution of NADPH oxidase inhibitors: selectivity and mechanisms for target engagement. Antioxid Redox Signal 23: 406–427, 2015.
6. Ameshima S, Golpon H, Cool CD, Chan D, Vandivier RW, Gardai SJ, Wick M, Nemenoff RA, Geraci MW, and Voelkel NF. Peroxisome proliferator-activated receptor gamma (PPARgamma) expression is decreased in pulmonary hypertension and affects endothelial cell growth. Circ Res 92: 1162–1169, 2003.
7. Archer SL, Weir EK, and Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation 121: 2045–2066, 2010.
8. Arciniegas E, Frid MG, Douglas IS, and Stenmark KR. Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 293: L1–L8, 2007.
9. Arciniegas E, Sutton AB, Allen TD, and Schor AM. Transforming growth factor beta 1 promotes the differentiation of endothelial cells into smooth muscle-like cells in vitro. J Cell Sci 103: 521–529, 1992.
10. Atkins K, Dasgupta A, Chen K-H, Mewburn J, and Archer SL. The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease. Clin Sci 130: 1861–1874, 2016.
11. ATS. International consensus conferences in intensive care medicine: ventilator-associated Lung Injury in ARDS. This official conference report was cosponsored by the American Thoracic Society, The European Society of Intensive Care Medicine, and The Societe de Reanimation de Langue Francaise, and was approved by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 160: 2118–2124, 1999.
12. Barbieri SS, Amadio P, Gianellini S, Zacchi E, Weksler BB, and Tremoli E. Tobacco smoke regulates the expression and activity of microsomal prostaglandin E synthase-1: role of prostacyclin and NADPH-oxidase. FASEB J 25: 3731–3740, 2011.
13. Barker AJ, Roldán-Alzate A, Entezari P, Shah SJ, Chesler NC, Wieben O, Markl M, and François CJ. Four-dimensional flow assessment of pulmonary artery flow and wall shear stress in adult pulmonary arterial hypertension: results from two institutions. Magn Reson Med 73: 1904–1913, 2015.
14. Barman SA, Chen F, Su Y, Dimitropoulou C, Wang Y, Catravas JD, Han W, Orfi L, Szantai-Kis C, Keri G, Szabadkai I, Barabutis N, Rafikova O, Rafikov R, Black SM, Jonigk D, Giannis A, Asmis R, Stepp DW, Ramesh G, and Fulton DJ. NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling. Arterioscler Thromb Vasc Biol 34: 1704–1715, 2014.
15. Bertero T, Cottrill K, Krauszman A, Lu Y, Annis S, Hale A, Bhat B, Waxman AB, Chau BN, Kuebler WM, and Chan SY. The microRNA-130/301 family controls vasoconstriction in pulmonary hypertension. J Biol Chem 290: 2069–2085, 2015.
16. Bertero T, Lu Y, Annis S, Hale A, Bhat B, Saggar R, Saggar R, Wallace WD, Ross DJ, Vargas SO, Graham BB, Kumar R, Black SM, Fratz S, Fineman JR, West JD, Haley KJ, Waxman AB, Chau BN, Cottrill KA, and Chan SY. Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension. J Clin Invest 124: 3514–3528, 2014.
17. Beyer AM. de Lange WJ, Halabi CM, Modrick ML, Keen HL, Faraci FM, and Sigmund CD. Endothelium-specific interference with peroxisome proliferator activated receptor gamma causes cerebral vascular dysfunction in response to a high-fat diet. Circ Res 103: 654–661, 2008.
18. Biancardi VC, Bomfim GF, Reis WL, Al-Gassimi S, and Nunes KP. The interplay between angiotensin II, TLR4 and hypertension. Pharmacol Res 120: 88–96, 2017.
19. Bienertova-Vasku J, Novak J, and Vasku A. MicroRNAs in pulmonary arterial hypertension: pathogenesis, diagnosis and treatment. J Am Soc Hypertens 9: 221–234, 2015.
20. Birukov KG. Cyclic stretch, reactive oxygen species, and vascular remodeling. Antioxid Redox Signal 11: 1651–1667, 2009.
21. Birukova AA, Fu P, Xing J, Cokic I, and Birukov KG. Lung endothelial barrier protection by iloprost in the 2-hit models of ventilator-induced lung injury (VILI) involves inhibition of Rho signaling. Transl Res 155: 44–54, 2010.
22. Birukova AA, Moldobaeva N, Xing J, and Birukov KG. Magnitude-dependent effects of cyclic stretch on HGF- and VEGF-induced pulmonary endothelial remodeling and barrier regulation. Am J Physiol Lung Cell Mol Physiol 295: L612–L623, 2008.
23. Birukova AA, Tian Y, Meliton A, Leff A, Wu T, and Birukov KG. Stimulation of Rho signaling by pathologic mechanical stretch is a “second hit” to Rho-independent lung injury induced by IL-6. Am J Physiol Lung Cell Mol Physiol 1: L965–L975, 2012.
24. Black SM, Field-Ridley A, Sharma S, Kumar S, Keller RL, Kameny R, Maltepe E, Datar SA, and Fineman JR. Altered carnitine homeostasis in children with increased pulmonary blood flow due to ventricular septal defects. Pediatr Crit Care Med 18: 931–934, 2017.
25. Blakely PK, Huber AK, and Irani DN. Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice. J Neuroinflamm 13: 196, 2016.
26. Block ER, Herrera H, and Couch M. Hypoxia inhibits L-arginine uptake by pulmonary artery endothelial cells. Am J Physiol 269: L574–L580, 1995.
27. Bodin P and Burnstock G. Evidence that release of adenosine triphosphate from endothelial cells during increased shear stress is vesicular. J Cardiovasc Pharmacol 2001: 900–908, 2001.
28. Boehme J, Sun X, Tormos KV, Gong W, Kellner M, Datar SA, Kameny RJ, Yuan JX, Raff GW, Fineman JR, Black SM, and Maltepe E. Pulmonary artery smooth muscle cell hyperproliferation and metabolic shift triggered by pulmonary overcirculation. Am J Physiol Heart Circ Physiol 311: H944–H957, 2016.
29. Böger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “L-arginine paradox” and acts as a novel cardiovascular risk factor. J Nutr 134: 2842S–2847S; discussion 2853S, 2004.
30. Boo YC, Hwang J, Sykes M, Michell BJ, Kemp BE, Lum H, and Jo H. Shear stress stimulates phosphorylation of eNOS at Ser635 by a protein kinase A-dependent mechanism. Am J Physiol Heart Circ Physiol 283: H1819–H1828, 2002.
31. Boo YC and Jo H. Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am J Physiol Cell Physiol 285: C499–C508, 2003.
32. Boo YC, Sorescu G, Bauer PM, Fulton D, Kemp BE, Harrison DG, Sessa WC, and Jo H. Phosphorylation of eNOS at Ser635 stimulates NO production in a Ca2+-independent manner. Free Radic Biol Med 35: 729–741, 2003.
33. Boon RA and Horrevoets AJ. Key transcriptional regulators of the vasoprotective effects of shear stress. Hamostaseologie 29: 39–40, 41–43, 2009.
34. Brand CS, Tan VP, Brown JH, and Miyamoto S. RhoA regulates Drp1 mediated mitochondrial fission through ROCK to protect cardiomyocytes. Cell Signal 50: 48–57, 2018.
35. Bretón-Romero R, Acín-Perez R, Rodríguez-Pascual F, Martínez-Molledo M, Brandes RP, Rial E, Enríquez JA, and Lamas S. Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta 1843: 2403–2413, 2014.
36. Brooks C, Cho SG, Wang CY, Yang T, and Dong Z. Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis. Am J Physiol Cell Physiol 300: C447–C455, 2011.
37. Buvinic S, Briones R, and Huidobro-Toro JP. P2Y1 and P2Y2 receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed. Br J Pharmacol 136: 847–856, 2002.
38. Buvinic S, Poblete MI, Donoso MV, Delpiano AM, Briones R, Miranda R, and Huidobro-Toro JP. P2Y1 and P2Y2 receptor distribution varies along the human placental vascular tree: role of nucleotides in vascular tone regulation. J Physiol 573: 427–443, 2006.
39. Cai H, McNally JS, Weber M, and Harrison DG. Oscillatory shear stress upregulation of endothelial nitric oxide synthase requires intracellular hydrogen peroxide and CaMKII. J Mol Cell Cardiol 37: 121–125, 2004.
40. Campbell WB, Gebremedhin D, Pratt PF, and Harder DR. Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ Res 78: 415–423, 1996.
41. Cantó C and Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20: 98–105, 2009.
42. Cao Z, Zhu H, Zhang L, Zhao X, Zweier JL, and Li Y. Antioxidants and phase 2 enzymes in cardiomyocytes: chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury. Exp Biol Med (Maywood) 231: 1353–1364, 2006.
43. Carvajal JA, Germain AM, Huidobro-Toro JP, and Weiner CP. Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol 184: 409–420, 2000.
44. Cerveny KL, Tamura Y, Zhang Z, Jensen RE, and Sesaki H. Regulation of mitochondrial fusion and division. Trends Cell Biol 17: 563–569, 2007.
45. Chai Q, Wang XL, Zeldin DC, and Lee HC. Role of caveolae in shear stress-mediated endothelium-dependent dilation in coronary arteries. Cardiovasc Res 100: 151–159, 2013.
46. Chan DC. Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22: 79–99, 2006.
47. Chang YC, Nalbant P, Birkenfeld J, Chang ZF, and Bokoch GM. GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA. Mol Biol Cell 19: 2147–2153, 2008.
48. Channick RN, Sitbon O, Barst RJ, Manes A, and Rubin LJ. Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol 43: 62S–67S, 2004.
49. Chao Y, Ye P, Zhu L, Kong X, Qu X, Zhang J, Luo J, Yang H, and Chen S. Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway. J Cell Physiol 233: 1384–1395, 2018.
50. Chen C, Gao JL, Liu MY, Li SL, Xuan XC, Zhang XZ, Zhang XY, Wei YY, Zhen CL, Jin J, Shen X, and Dong DL. Mitochondrial fission inhibitors suppress endothelin-1-induced artery constriction. Cell Physiol Biochem 42: 1802–1811, 2017.
51. Chen F, Kumar S, Yu Y, Aggarwal S, Gross C, Wang Y, Chakraborty T, Verin AD, Catravas JD, Lucas R, Black SM, and Fulton DJ. PKC-dependent phosphorylation of eNOS at T495 regulates eNOS coupling and endothelial barrier function in response to G+-toxins. PLoS One 9: e99823, 2014.
52. Chen H and Chan DC. Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14(Spec No. 2): R283–R289, 2005.
53. Chen K, Fan W, Wang X, Ke X, Wu G, and Hu C. MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells. Biochem Biophys Res Commun 427: 138–142, 2012.
54. Chen KH, Dasgupta A, Lin J, Potus F, Bonnet S, Iremonger J, Fu J, Mewburn J, Wu D, Dunham-Snary K, Theilmann AL, Jing ZC, Hindmarch C, Ormiston ML, Lawrie A, and Archer SL. Epigenetic dysregulation of the dynamin-related protein binding partners MiD49 and MiD51 increases mitotic mitochondrial fission and promotes pulmonary arterial hypertension: mechanistic and therapeutic implications. Circulation 138: 287–304, 2018.
55. Chen W, Epshtein Y, Ni X, Dull RO, Cress AE, Garcia JGN, and Jacobson JR. Role of Integrin β4 in lung endothelial cell inflammatory responses to mechanical stress. Sci Rep 5: 16529, 2015.
56. Chen W, Garcia JG, and Jacobson JR. Integrin beta4 attenuates SHP-2 and MAPK signaling and reduces human lung endothelial inflammatory responses. J Cell Biochem 1: 718–724, 2010.
57. Chen W, Sammani S, Mitra S, Ma SF, Garcia JG, and Jacobson JR. Critical role for integrin-β4 in the attenuation of murine acute lung injury by simvastatin. Am J Physiol Lung Cell Mol Physiol 303: L279–L285, 2012.
58. Chen XY, Dun JN, Miao QF, and Zhang YJ. Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, suppresses 5-hydroxytryptamine-induced pulmonary artery smooth muscle cell proliferation via JNK and ERK1/2 pathway. Pharmacology 83: 67–79, 2009.
59. Chen Z, Peng IC, Cui X, Li YS, Chien S, and Shyy JY. Shear stress, SIRT1, and vascular homeostasis. Proc Natl Acad Sci U S A 107: 10268–10273, 2010.
60. Cheng M, Liu X, Li Y, Tang R, Zhang W, Wu J, Li L, Liu X, Gang Y, and Chen H. IL-8 gene induction by low shear stress: pharmacological evaluation of the role of signaling molecules. Biorheology 44: 349–360, 2007.
61. Cheng M, Wu J, Li Y, Nie Y, and Chen H. Activation of MAPK participates in low shear stress-induced IL-8 gene expression in endothelial cells. Clin Biomech Bristol Avon 23(Suppl. 1): S96–S103, 2008.
62. Cheng M, Wu J, Liu X, Li Y, Nie Y, Li L, and Chen H. Low shear stress-induced interleukin-8 mRNA expression in endothelial cells is mechanotransduced by integrins and the cytoskeleton. Endothelium 14: 265–273, 2007.
63. Chow KB, Jones RL, and Wise H. Protein kinase A-dependent coupling of mouse prostacyclin receptors to Gi is cell-type dependent. Eur J Pharmacol 474: 7–13, 2003.
64. Cifuentes-Pagano E, Csanyi G, and Pagano PJ. NADPH oxidase inhibitors: a decade of discovery from Nox2ds to HTS. Cell Mol Life Sci 69: 2315–2325, 2012.
65. Coleman HA, Tare M, and Parkington HC. Myoendothelial electrical coupling in arteries and arterioles and its implications for endothelium-derived hyperpolarizing factor. Clin Exp Pharmacol Physiol 29: 630–637, 2002.
66. Coleman RA, Smith WL, and Narumiya S. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46: 205–229, 1994.
67. Cornwell TL, Arnold E, Boerth NJ, and Lincoln TM. Inhibition of smooth muscle cell growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP. Am J Physiol 267: C1405–C1413, 1994.
68. Courboulin A, Paulin R, Giguère NJ, Saksouk N, Perreault T, Meloche J, Paquet ER, Biardel S, Provencher S, Côté J, Simard MJ, and Bonnet S. Role for miR-204 in human pulmonary arterial hypertension. J Exp Med 208: 535–548, 2011.
69. Cowburn AS, Crosby A, Macias D, Branco C, Colaço RD, Southwood M, Toshner M, Crotty Alexander LE, Morrell NW, Chilvers ER, and Johnson RS. HIF2alpha-arginase axis is essential for the development of pulmonary hypertension. Proc Natl Acad Sci U S A 113: 8801–8806, 2016.
70. Czikora I, Alli AA, Sridhar S, Matthay MA, Pillich H, Hudel M, Berisha B, Gorshkov B, Romero MJ, Gonzales J, Wu G, Huo Y, Su Y, Verin AD, Fulton D, Chakraborty T, Eaton DC, and Lucas R. Epithelial sodium channel-α mediates the protective effect of the TNF-derived TIP peptide in pneumolysin-induced endothelial barrier dysfunction. Front Immunol 8: 842, 2017.
71. Czikora I, Sridhar S, Gorshkov B, Alieva IB, Kasa A, Gonzales J, Potapenko O, Umapathy NS, Pillich H, Rick FG, Block NL, Verin AD, Chakraborty T, Matthay MA, Schally AV, and Lucas R. Protective effect of growth hormone-releasing hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction. Front Physiol 5: 259, 2014.
72. Davenport AP and Maguire JJ. Endothelin. Handb Exp Pharmacol (176 Pt 1): 295–329, 2006.
73. David V, Succar B, de Moraes JA, Saldanha-Gama RFG, Barja-Fidalgo C, and Zingali RB. Recombinant and chimeric disintegrins in preclinical research. Toxins (Basel) 10: pii:, 2018.
74. Davie N, Haleen SJ, Upton PD, Polak JM, Yacoub MH, Morrell NW, and Wharton J. ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med 165: 398–405, 2002.
75. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 75: 519–560, 1995.
76. Davis ME, Cai H, Drummond GR, and Harrison DG. Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways. Circ Res 89: 1073–1080, 2001.
77. De Mey JG and Vanhoutte PM. End o' the line revisited: moving on from nitric oxide to CGRP. Life Sci 118: 120–128, 2014.
78. Deng Y, Lei T, Li H, Mo X, Wang Z, and Ou H. ERK5/KLF2 activation is involved in the reducing effects of puerarin on monocyte adhesion to endothelial cells and atherosclerotic lesion in apolipoprotein E-deficient mice. Biochim Biophys Acta 1864: 2590–2599, 2018.
79. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, and Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399: 601–605, 1999.
80. Doehner W, Schoene N, Rauchhaus M, Leyva-Leon F, Pavitt DV, Reaveley DA, Schuler G, Coats AJ, Anker SD, and Hambrecht R. Effects of xanthine oxidase inhibition with allopurinol on endothelial function and peripheral blood flow in hyperuricemic patients with chronic heart failure: results from 2 placebo-controlled studies. Circulation 105: 2619–2624, 2002.
81. Dolinay T, Wu W, Kaminski N, Ifedigbo E, Kaynar AM, Szilasi M, Watkins SC, Ryter SW, Hoetzel A, and Choi AM. Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury. PLoS One 3: e1601, 2008.
82. Duerrschmidt N, Stielow C, Muller G, Pagano PJ, and Morawietz H. NO-mediated regulation of NAD(P)H oxidase by laminar shear stress in human endothelial cells. J Physiol 576: 557–567, 2006.
83. Dugan LL, You YH, Ali SS, Diamond-Stanic M, Miyamoto S, DeCleves AE, Andreyev A, Quach T, Ly S, Shekhtman G, Nguyen W, Chepetan A, Le TP, Wang L, Xu M, Paik KP, Fogo A, Viollet B, Murphy A, Brosius F, Naviaux RK, and Sharma K. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 123: 4888–4899, 2013.
84. Edwards G, Dora KA, Gardener MJ, Garland CJ, and Weston AH. K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 396: 269–272, 1998.
85. Edwards G, Félétou M, and Weston AH. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch 459: 863–879, 2010.
86. Ellinsworth DC, Earley S, Murphy TV, and Sandow SL. Endothelial control of vasodilation: integration of myoendothelial microdomain signalling and modulation by epoxyeicosatrienoic acids. Pflugers Arch 466: 389–405, 2014.
87. Engelfriet PM, Duffels MG, Möller T, Boersma E, Tijssen JG, Thaulow E, Gatzoulis MA, and Mulder BJ. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart 93: 682–687, 2007.
88. Ercan S, Cakmak A, Kösecik M, and Erel O. The oxidative state of children with cyanotic and acyanotic congenital heart disease. Anadolu Kardiyol Derg 9: 486–490, 2009.
89. Fan W, Fang R, Wu X, Liu J, Feng M, Dai G, Chen G, and Wu G. Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial inflammation. J Cell Sci 128: 70–80, 2015.
90. Fang Y and Davies PF. Site-specific microRNA-92a regulation of Kruppel-like factors 4 and 2 in atherosusceptible endothelium. Arterioscler Thromb Vasc Biol 32: 979–987, 2012.
91. Fang ZF, Huang YY, Tang L, Hu XQ, Shen XQ, Tang JJ, and Zhou SH. Asymmetric dimethyl-l-arginine is a biomarker for disease stage and follow-up of pulmonary hypertension associated with congenital heart disease. Pediatr Cardiol 36: 1062–1069, 2015.
92. Félétou M and Vanhoutte PM. EDHF: an update. Clin Sci (Lond) 117: 139–155, 2009.
93. Feng M, Liu L, Guo Z, and Xiong Y. Gene transfer of dimethylarginine dimethylaminohydrolase-2 improves the impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells induced by lysophosphatidylcholine. Eur J Pharmacol 584: 49–56, 2008.
94. Fisslthaler B, Dimmeler S, Hermann C, Busse R, and Fleming I. Phosphorylation and activation of the endothelial nitric oxide synthase by fluid shear stress. Acta Physiol 168: 81–88, 2000.
95. Fledderus JO, Boon RA, Volger OL, Hurttila H, Ylä-Herttuala S, Pannekoek H, Levonen AL, and Horrevoets AJ. KLF2 primes the antioxidant transcription factor Nrf2 for activation in endothelial cells. Arterioscler Thromb Vasc Biol 28: 1339–1346, 2008.
96. Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, and Busse R. Phosphorylation of Thr495 regulates Ca2+/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res 88: E68–E75, 2001.
97. Frazziano G, Al Ghouleh I, Baust J, Shiva S, Champion HC, and Pagano PJ. Nox-derived ROS are acutely activated in pressure overload pulmonary hypertension: indications for a seminal role for mitochondrial Nox4. Am J Physiol Heart Circ Physiol 306: H197–H205, 2014.
98. Frid MG, Kale VA, and Stenmark KR. Mature vascular endothelium can give rise to smooth muscle cells via endothelial-mesenchymal transdifferentiation: in vitro analysis. Circ Res 90: 1189–1196, 2002.
99. Friedl HP, Till GO, Ryan US, and Ward PA. Mediator-induced activation of xanthine oxidase in endothelial cells. FASEB J 3: 2512–2518, 1989.
100. Fu Y, Zhang Y, Wang Z, Wang L, Wei X, Zhang B, Wen Z, Fang H, Pang Q, and Yi F. Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. Am J Nephrol 32: 581–589, 2010.
101. Galiè N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, Klepetko W, McGoon MD, McLaughlin VV, Preston IR, Rubin LJ, Sandoval J, Seeger W, and Keogh A. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol 62: D60–D72, 2013.
102. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, and Hoeper M. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Rev Esp Cardiol (Engl Ed) 69: 177, 2016.
103. Galougahi KK, Liu CC, Gentile C, Kok C, Nunez A, Garcia A, Fry NA, Davies MJ, Hawkins CL, Rasmussen HH, and Figtree GA. Glutathionylation mediates angiotensin II-induced eNOS uncoupling, amplifying NADPH oxidase-dependent endothelial dysfunction. J Am Heart Assoc 3: e000731, 2014.
104. García-Cardeña G, Fan R, Stern DF, Liu J, and Sessa WC. Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1. J Biol Chem 271: 27237–27240, 1996.
105. Gatzoulis MA, Alonso-Gonzalez R, and Beghetti M. Pulmonary arterial hypertension in paediatric and adult patients with congenital heart disease. Eur Respir Rev 18: 154–161, 2009.
106. Gawlak G, Tian Y, O'Donnell JJ 3rd, Tian X, Birukova AA, and Birukov KG. Paxillin mediates stretch-induced Rho signaling and endothelial permeability via assembly of paxillin-p42/44MAPK-GEF-H1 complex. FASEB J 28: 3249–3260, 2014.
107. Giaid A, Yanagisawa M, Langleben D, Michel RP, Levy R, Shennib H, Kimura S, Masaki T, Duguid WP, and Stewart DJ. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 328: 1732–1739, 1993.
108. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, and Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 127: e6–e245, 2013.
109. Goedicke-Fritz S, Kaistha A, Kacik M, Markert S, Hofmeister A, Busch C, Bänfer S, Jacob R, Grgic I, and Hoyer J. Evidence for functional and dynamic microcompartmentation of Cav-1/TRPV4/K(Ca) in caveolae of endothelial cells. Eur J Cell Biol 94: 391–400, 2015.
110. Goettsch C, Goettsch W, Brux M, Haschke C, Brunssen C, Muller G, Bornstein SR, Duerrschmidt N, Wagner AH, and Morawietz H. Arterial flow reduces oxidative stress via an antioxidant response element and Oct-1 binding site within the NADPH oxidase 4 promoter in endothelial cells. Basic Res Cardiol 106: 551–561, 2011.
111. Gosgnach W, Challah M, Coulet F, Michel JB, and Battle T. Shear stress induces angiotensin converting enzyme expression in cultured smooth muscle cells: possible involvement of bFGF. Cardiovasc Res 45: 486–492, 2000.
112. Gross CM, Rafikov R, Kumar S, Aggarwal S, Ham PB 3rd, Meadows ML, Cherian-Shaw M, Kangath A, Sridhar S, Lucas R, and Black SM. Endothelial nitric oxide synthase deficient mice are protected from lipopolysaccharide induced acute lung injury. PLoS One 10: e0119918, 2015.
113. Gupte SA, Okada T, and Ochi R. Superoxide and nitroglycerin stimulate release of PGF2 alpha and TxA2 in isolated rat heart. Am J Physiol 271: H2447–H2453, 1996.
114. Gupte SA, Okada T, Tateyama M, and Ochi R. Activation of TxA2/PGH2 receptors and protein kinase C contribute to coronary dysfunction in superoxide treated rat hearts. J Mol Cell Cardiol 32: 937–946, 2000.
115. Hall AR, Burke N, Dongworth RK, and Hausenloy DJ. Mitochondrial fusion and fission proteins: novel therapeutic targets for combating cardiovascular disease. Br J Pharmacol 171: 1890–1906, 2014.
116. Han Z, Chen YR, Jones CI, 3rd, Meenakshisundaram G, Zweier JL, and Alevriadou BR. Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex activities in cultured vascular endothelial cells. Am J Physiol Cell Physiol 292: C1103–C1112, 2007.
117. Haque R, Chun E, Howell JC, Sengupta T, Chen D, and Kim H. MicroRNA-30b-mediated regulation of catalase expression in human ARPE-19 cells. PLoS One 7: e42542, 2012.
118. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, and Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A 105: 1516–1521, 2008.
119. Harris TA, Yamakuchi M, Kondo M, Oettgen P, and Lowenstein CJ. Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler Thromb Vasc Biol 30: 1990–1997, 2010.
120. Haworth SG. Pulmonary vascular disease in different types of congenital heart disease. Implications for interpretation of lung biopsy findings in early childhood. Br Heart J 52: 557–571, 1984.
121. Hjortshøj CMS, Kempny A, Jensen AS, Sørensen K, Nagy E, Dellborg M, Johansson B, Rudiene V, Hong G, Opotowsky AR, Budts W, Mulder BJ, Tomkiewicz-Pajak L, D'Alto M, Prokšelj K, Diller GP, Dimopoulos K, Estensen ME, Holmstrøm H, Turanlahti M, Thilén U, Gatzoulis MA, and Søndergaard L. Past and current cause-specific mortality in Eisenmenger syndrome. Eur Heart J 38: 2060–2067, 2017.
122. Hoffman JI and Rudolph AM. The natural history of ventricular septal defects in infancy. Am J Cardiol 16: 634–653, 1965.
123. Hoffman JI and Rudolph AM. The natural history of isolated ventricular septal defect with special reference to selection of patients for surgery. Adv Pediatr 17: 57–79, 1970.
124. Hoffman JI, Rudolph AM, and Danilowicz D. Left to right atrial shunts in infants. Am J Cardiol 30: 868–875, 1972.
125. Holliday CJ, Ankeny RF, Jo H, and Nerem RM. Discovery of shear- and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells. Am J Physiol Heart Circ Physiol 301: H856–H867, 2011.
126. Hu C, Lu KT, Mukohda M, Davis DR, Faraci FM, and Sigmund CD. Interference with PPARγ in endothelium accelerates angiotensin II-induced endothelial dysfunction. Physiol Genomics 48: 124–134, 2016.
127. Huang W, Sakamoto N, Miyazawa R, and Sato M. Role of paxillin in the early phase of orientation of the vascular endothelial cells exposed to cyclic stretching. Biochem Biophys Res Commun 418: 708–713, 2012.
128. Humphries MJ, Travis MA, Clark K, and Mould AP. Mechanisms of integration of cells and extracellular matrices by integrins. Biochem Soc Trans 32: 822–825, 2004.
129. Hwang SA, Boo YC, Sorescu GP, McNally JS, Holland SM, Dikalov S, Giddens DP, Griendling KK, Harrison DG, and Jo H. Oscillatory shear stress stimulates endothelial production of O2− from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion. J Biol Chem 278: 47291–47298, 2003.
130. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 110: 673–687, 2002.
131. Ikeda Y, Shirakabe A, Brady C, Zablocki D, Ohishi M, and Sadoshima J. Molecular mechanisms mediating mitochondrial dynamics and mitophagy and their functional roles in the cardiovascular system. J Mol Cell Cardiol 78: 116–122, 2015.
132. Ishikawa K, Navab M, Leitinger N, Fogelman AM, and Lusis AJ. Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL. J Clin Invest 100: 1209–1216, 1997.
133. Ishimitsu T, Uehara Y, Ishii M, Ikeda T, Matsuoka H, and Sugimoto T. Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats. Hypertension 12: 46–51, 1988.
134. Ismail S, Sturrock A, Wu P, Cahill B, Norman K, Huecksteadt T, Sanders K, Kennedy T, and Hoidal J. NOX4 mediates hypoxia-induced proliferation of human pulmonary artery smooth muscle cells: the role of autocrine production of transforming growth factor-{beta}1 and insulin-like growth factor binding protein-3. Am J Physiol Lung Cell Mol Physiol 296: L489–L499, 2009.
135. Jahani-Asl A and Slack RS. The phosphorylation state of Drp1 determines cell fate. EMBO Rep 8: 912–913, 2007.
136. Jeremy JY, Rowe D, Emsley AM, and Newby AC. Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res 43: 580–594, 1999.
137. Ji Y, Wang Z, Li Z, Zhang A, Jin Y, Chen H, and Le X. Angiotensin II enhances proliferation and inflammation through AT1/PKC/NF-kappaB signaling pathway in hepatocellular carcinoma cells. Cell Physiol Biochem 39: 13–32, 2016.
138. Jones CI 3rd, Zhu H, Martin SF, Han Z, Li Y, and Alevriadou BR. Regulation of antioxidants and phase 2 enzymes by shear-induced reactive oxygen species in endothelial cells. Ann Biomed Eng 35: 683–693, 2007.
139. Jornayvaz FR and Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem 47: 69–84, 2010.
140. Kang BY, Park KK, Kleinhenz JM, Murphy TC, Green DE, Bijli KM, Yeligar SM, Carthan KA, Searles CD, Sutliff RL, and Hart CM. Peroxisome proliferator-activated receptor γ and microRNA 98 in hypoxia-induced endothelin-1 signaling. Am J Respir Cell Mol Biol 54: 136–146, 2016.
141. Katusić ZS, Schugel J, Cosentino F, and Vanhoutte PM. Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery. Am J Physiol 264: H859–H864, 1993.
142. Kidd L, Driscoll DJ, Gersony WM, Hayes CJ, Keane JF, O'Fallon WM, Pieroni DR, Wolfe RR, and Weidman WH. Second natural history study of congenital heart defects. Results of treatment of patients with ventricular septal defects. Circulation 87: I38–I51, 1993.
143. Kim JS, Kim B, Lee H, Thakkar S, Babbitt DM, Eguchi S, Brown MD, and Park JY. Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells. Am J Physiol Heart Circ Physiol 309: H425–H433, 2015.
144. Kim M, Kim S, Lim JH, Lee C, Choi HC, and Woo CH. Laminar flow activation of ERK5 protein in vascular endothelium leads to atheroprotective effect via NF-E2-related factor 2 (Nrf2) activation. J Biol Chem 287: 40722–40731, 2012.
145. Kratzer E, Tian Y, Sarich N, Wu T, Meliton A, Leff A, and Birukova AA. Oxidative stress contributes to lung injury and barrier dysfunction via microtubule destabilization. Am J Respir Cell Mol Biol 47: 688–697, 2012.
146. Krotova K, Patel JM, Block ER, and Zharikov S. Hypoxic upregulation of arginase II in human lung endothelial cells. Am J Physiol Cell Physiol 299: C1541–C1548, 2010.
147. Kubes P, Suzuki M, and Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A 88: 4651–4655, 1991.
148. Kuipers AJ, Middelbeek J, and van Leeuwen FN. Mechanoregulation of cytoskeletal dynamics by TRP channels. Eur J Cell Biol 91: 834–846, 2012.
149. Kumar S, Sun X, Noonepalle SK, Lu Q, Zemskov E, Wang T, Aggarwal S, Gross C, Sharma S, Desai AA, Hou Y, Dasarathy S, Qu N, Reddy V, Lee SG, Cherian-Shaw M, Yuan JX, Catravas JD, Rafikov R, Garcia JGN, and Black SM. Hyper-activation of pp60Src limits nitric oxide signaling by increasing asymmetric dimethylarginine levels during acute lung injury. Free Radic Biol Med 102: 217–228, 2017.
150. Lakier JB, Stanger P, Heymann MA, HoffmaN JI, and Rudolph AM. Early onset of pulmonary vascular obstruction in patients with aortopulmonary transposition and intact ventricular septum. Circulation 51: 875–880, 1975.
151. Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C, Harrison DG, Hornig B, and Drexler H. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation 106: 3073–3078, 2002.
152. Lassègue B San Martín A, and Griendling KK. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110: 1364–1390, 2012.
153. Le A, Damico R, Damarla M, Boueiz A, Pae HH, Skirball J, Hasan E, Peng X, Chesley A, Crow MT, Reddy SP, Tuder RM, and Hassoun PM. Alveolar cell apoptosis is dependent on p38 MAP kinase-mediated activation of xanthine oxidoreductase in ventilator-induced lung injury. J Appl Physiol (1985) 105: 1282–1290, 2008.
154. Lee DY, Lin TE, Lee CI, Zhou J, Huang YH, Lee PL, Shih YT, Chien S, and Chiu JJ. MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases. Proc Natl Acad Sci U S A 114: 2072–2077, 2017.
155. This reference has been deleted.
156. Lee DY, Yang TL, Huang YH, Lee CI, Chen LJ, Shih YT, Wei SY, Wang WL, Wu CC, and Chiu JJ. Induction of microRNA-10a using retinoic acid receptor-α and retinoid x receptor-α agonists inhibits atherosclerotic lesion formation. Atherosclerosis 271: 36–44, 2018.
157. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, and Burge CB. Prediction of mammalian microRNA targets. Cell 115: 787–798, 2003.
158. Li MX and Dewson G. Mitochondria and apoptosis: emerging concepts. F1000 Prime Rep 7: 42, 2015.
159. Li S, Tabar SS, Malec V, Eul BG, Klepetko W, Weissmann N, Grimminger F, Seeger W, Rose F, and Hänze J. NOX4 regulates ROS levels under normoxic and hypoxic conditions, triggers proliferation, and inhibits apoptosis in pulmonary artery adventitial fibroblasts. Antioxid Redox Signal 10: 1687–1698, 2008.
160. Li X, Yu Y, Gorshkov B, Haigh S, Bordan Z, Weintraub D, Rudic RD, Chakraborty T, Barman SA, Verin AD, Su Y, Lucas R, Stepp DW, Chen F, and Fulton DJR. Hsp70 suppresses mitochondrial reactive oxygen species and preserves pulmonary microvascular barrier integrity following exposure to bacterial toxins. Front Immunol 9: 1309, 2018.
161. Li Y, Zheng J, Bird IM, and Magness RR. Mechanisms of shear stress-induced endothelial nitric-oxide synthase phosphorylation and expression in ovine fetoplacental artery endothelial cells. Biol Reprod 70: 785–796, 2004.
162. Liu LH, Guo Z, Feng M, Wu ZZ, He ZM, and Xiong Y. Protection of DDAH2 overexpression against homocysteine-induced impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells. Cell Physiol Biochem 30: 1413–1422, 2012.
163. Liu SY, Duan XC, Jin S, Teng X, Xiao L, Xue HM, and Wu YM. Hydrogen sulfide improves myocardial remodeling via downregulated angiotensin II/AT1R pathway in renovascular hypertensive rats. Am J Hypertens 30: 67–74, 2017.
164. Loyer X, Potteaux S, Vion AC, Guérin CL, Boulkroun S, Rautou PE, Ramkhelawon B, Esposito B, Dalloz M, Paul JL, Julia P, Maccario J, Boulanger CM, Mallat Z, and Tedgui A. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res 114: 434–443, 2014.
165. Lu T, Wang XL, Chai Q, Sun X, Sieck GC, Katusic ZS, and Lee HC. Role of the endothelial caveolae microdomain in shear stress-mediated coronary vasorelaxation. J Biol Chem 292: 19013–19023, 2017.
166. Lu X and Kassab GS. Nitric oxide is significantly reduced in ex vivo porcine arteries during reverse flow because of increased superoxide production. J Physiol 561: 575–582, 2004.
167. Lucas R, Sridhar S, Rick FG, Gorshkov B, Umapathy NS, Yang G, Oseghale A, Verin AD, Chakraborty T, Matthay MA, Zemskov EA, White R, Block NL, and Schally AV. Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema. Proc Natl Acad Sci U S A 109: 2084–2089, 2012.
168. Lucas R, Yang G, Gorshkov BA, Zemskov EA, Sridhar S, Umapathy NS, Jezierska-Drutel A, Alieva IB, Leustik M, Hossain H, Fischer B, Catravas JD, Verin AD, Pittet JF, Caldwell RB, Mitchell TJ, Cederbaum SD, Fulton DJ, Matthay MA, Caldwell RW, Romero MJ, and Chakraborty T. Protein kinase C-alpha and arginase I mediate pneumolysin-induced pulmonary endothelial hyperpermeability. Am J Respir Cell Mol Biol 47: 445–453, 2012.
169. This reference has been deleted.
170. Macdonald PJ, Stepanyants N, Mehrotra N, Mears JA, Qi X, Sesaki H, and Ramachandran R. A dimeric equilibrium intermediate nucleates Drp1 reassembly on mitochondrial membranes for fission. Mol Biol Cell 25: 1905–1915, 2014.
171. Maitra U, Singh N, Gan L, Ringwood L, and Li L. IRAK-1 contributes to lipopolysaccharide-induced reactive oxygen species generation in macrophages by inducing NOX-1 transcription and Rac1 activation and suppressing the expression of antioxidative enzymes. J Biol Chem 284: 35403–35411, 2009.
172. Mammoto T, Muyleart M, Konduri GG, and Mammoto A. Twist1 in hypoxia-induced pulmonary hypertension through transforming growth factor-beta-Smad signaling. Am J Respir Cell Mol Biol 58: 194–207, 2018.
173. Mao X, Said R, Louis H, Max JP, Bourhim M, Challande P, Wahl D, Li Z, Regnault V, and Lacolley P. Cyclic stretch-induced thrombin generation by rat vascular smooth muscle cells is mediated by the integrin alphavbeta3 pathway. Cardiovasc Res 96: 513–523, 2012.
174. Marin T, Gongol B, Chen Z, Woo B, Subramaniam S, Chien S, and Shyy JY. Mechanosensitive microRNAs-role in endothelial responses to shear stress and redox state. Free Radic Biol Med 64: 61–68, 2013.
175. Marin TL, Gongol B, Zhang F, Martin M, Johnson DA, Xiao H, Wang Y, Subramaniam S, Chien S, and Shyy JY. AMPK promotes mitochondrial biogenesis and function by phosphorylating the epigenetic factors DNMT1, RBBP7, and HAT1. Sci Signal 10: pii:, 2017.
176. Martínez-Caro L, Lorente JA, Marín-Corral J, Sánchez-Rodríguez C, Sánchez-Ferrer A, Nin N, Ferruelo A, de Paula M, Fernández-Segoviano P, Barreiro E, and Esteban A. Role of free radicals in vascular dysfunction induced by high tidal volume ventilation. Intensive Care Med 35: 1110–1119, 2009.
177. Martínez-Caro L, Nin N, Sánchez-Rodríguez C, Ferruelo A, El Assar M, de Paula M, Fernández-Segoviano P, Esteban A, and Lorente JA. Inhibition of nitro-oxidative stress attenuates pulmonary and systemic injury induced by high-tidal volume mechanical ventilation. Shock 44: 36–43, 2015.
178. Masatsugu K, Itoh H, Chun TH, Ogawa Y, Tamura N, Yamashita J, Doi K, Inoue M, Fukunaga Y, Sawada N, Saito T, Korenaga R, Ando J, and Nakao K. Physiologic shear stress suppresses endothelin-converting enzyme-1 expression in vascular endothelial cells. J Cardiovasc Pharmacol 31(Suppl. 1): S42–S45, 1998.
179. Masatsugu K, Itoh H, Chun TH, Saito T, Yamashita J, Doi K, Inoue M, Sawada N, Fukunaga Y, Sakaguchi S, Sone M, Yamahara K, Yurugi T, and Nakao K. Shear stress attenuates endothelin and endothelin-converting enzyme expression through oxidative stress. Regul Pept 111: 13–19, 2003.
180. Mata-Greenwood E, Meyrick B, Steinhorn RH, Fineman JR, and Black SM. Alterations in TGF-beta1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 285: L209–L221, 2003.
181. Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, and Takeshita A. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest 106: 1521–1530, 2000.
182. Matrougui K, Maclouf J, Lévy BI, and Henrion D. Impaired nitric oxide- and prostaglandin-mediated responses to flow in resistance arteries of hypertensive rats. Hypertension 30: 942–947, 1997.
183. McNally JS, Davis ME, Giddens DP, Saha A, Hwang J, Dikalov S, Jo H, and Harrison DG. Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol 285: H2290–H2297, 2003.
184. Menghini R, Casagrande V, Cardellini M, Martelli E, Terrinoni A, Amati F, Vasa-Nicotera M, Ippoliti A, Novelli G, Melino G, Lauro R, and Federici M. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 120: 1524–1532, 2009.
185. Merino H, Parthasarathy S, and Singla DK. Partial ligation-induced carotid artery occlusion induces leukocyte recruitment and lipid accumulation—a shear stress model of atherosclerosis. Mol Cell Biochem 372: 267–273, 2013.
186. Michell BJ, Chen ZP, Tiganis T, Stapleton D, Katsis F, Power DA, Sim AT, and Kemp BE. Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem 276: 17625–17628, 2001.
187. Miller SB. Prostaglandins in health and disease: an overview. Semin Arthritis Rheum 36: 37–49, 2006.
188. Minuz P, Barrow SE, Cockcroft JR, and Ritter JM. Prostacyclin and thromboxane biosynthesis in mild essential hypertension. Hypertension 15: 469–474, 1990.
189. Miura H, Bosnjak JJ, Ning G, Saito T, Miura M, and Gutterman DD. Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles. Circ Res 92: e31–e40, 2003.
190. Mohan S, Koyoma K, Thangasamy A, Nakano H, Glickman RD, and Mohan N. Low shear stress preferentially enhances IKK activity through selective sources of ROS for persistent activation of NF-kappaB in endothelial cells. Am J Physiol Cell Physiol 292: C362–C371, 2007.
191. Morawietz H, Talanow R, Szibor M, Rueckschloss U, Schubert A, Bartling B, Darmer D, and Holtz J. Regulation of the endothelin system by shear stress in human endothelial cells. J Physiol 525(Pt 3): 761–770, 2000.
192. Mukohda M, Stump M, Ketsawatsomkron P, Hu C, Quelle FW, and Sigmund CD. Endothelial PPAR-gamma provides vascular protection from IL-1beta-induced oxidative stress. Am J Physiol Heart Circ Physiol 310: H39–H48, 2016.
193. Muzaffar S, Jeremy JY, Angelini GD, and Shukla N. NADPH oxidase 4 mediates upregulation of type 4 phosphodiesterases in human endothelial cells. J Cell Physiol 227: 1941–1950, 2012.
194. Nakahata N. Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther 118: 18–35, 2008.
195. Nakamura T and Lipton SA. Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer's and Parkinson's diseases. Apoptosis 15: 1354–1363, 2010.
196. Nam D, Ni CW, Rezvan A, Suo J, Budzyn K, Llanos A, Harrison D, Giddens D, and Jo H. Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis. Am J Physiol Heart Circ Physiol 297: H1535–H1543, 2009.
197. Nam D, Ni CW, Rezvan A, Suo J, Budzyn K, Llanos A, Harrison DG, Giddens DP, and Jo H. A model of disturbed flow-induced atherosclerosis in mouse carotid artery by partial ligation and a simple method of RNA isolation from carotid endothelium. J Vis Exp 40: 1861, 2010.
198. Ni CW, Qiu H, and Jo H. MicroRNA-663 upregulated by oscillatory shear stress plays a role in inflammatory response of endothelial cells. Am J Physiol Heart Circ Physiol 300: H1762–H1769, 2011.
199. Nicosia S, Oliva D, Noè MA, Corsini A, Folco GC, and Fumagalli R. PGI2 receptors in vasculature and platelets: 5Z-carbacyclin discriminates between them. Adv Prostaglandin Thromboxane Leukot Res 17A: 474–478, 1987.
200. O'Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jørgensen SB, Schertzer JD, Shyroka O, Kiens B, van Denderen BJ, Tarnopolsky MA, Kemp BE, Richter EA, and Steinberg GR. AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci U S A 108: 16092–16097, 2011.
201. O'Rourke MF. Vascular impedance in studies of arterial and cardiac function. Physiol Rev 62: 570–623, 1982.
202. Odagiri K, Inui N, Hakamata A, Inoue Y, Suda T, Takehara Y, Sakahara H, Sugiyama M, Alley MT, Wakayama T, and Watanabe H. Non-invasive evaluation of pulmonary arterial blood flow and wall shear stress in pulmonary arterial hypertension with 3D phase contrast magnetic resonance imaging. Springerplus 5: 1071, 2016.
203. Otera H, Ishihara N, and Mihara K. New insights into the function and regulation of mitochondrial fission. Biochim Biophys Acta 1833: 1256–1268, 2013.
204. Otto S, Deussen A, Zatschler B, Müller B, Neisser A, Barth K, Morawietz H, and Kopaliani I. A novel role of endothelium in activation of latent pro-membrane type 1 MMP and pro-MMP-2 in rat aorta. Cardiovasc Res 109: 409–418, 2016.
205. Pakala R, Willerson JT, and Benedict CR. Effect of serotonin, thromboxane A2, and specific receptor antagonists on vascular smooth muscle cell proliferation. Circulation 96: 2280–2286, 1997.
206. Pantos I, Patatoukas G, Efstathopoulos EP, and Katritsis D. In vivo wall shear stress measurements using phase-contrast MRI. Expert Rev Cardiovasc Ther 5: 927–938, 2007.
207. Park HS, Chun JN, Jung HY, Choi C, and Bae YS. Role of NADPH oxidase 4 in lipopolysaccharide-induced proinflammatory responses by human aortic endothelial cells. Cardiovasc Res 72: 447–455, 2006.
208. Park HS, Jung HY, Park EY, Kim J, Lee WJ, and Bae YS. Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B. J Immunol 173: 3589–3593, 2004.
209. Partridge J, Carlsen H, Enesa K, Chaudhury H, Zakkar M, Luong L, Kinderlerer A, Johns M, Blomhoff R, Mason JC, Haskard DO, and Evans PC. Laminar shear stress acts as a switch to regulate divergent functions of NF-kappaB in endothelial cells. FASEB J 21: 3553–3561, 2007.
210. Patel DN, Bailey SR, Gresham JK, Schuchman DB, Shelhamer JH, Goldstein BJ, Foxwell BM, Stemerman MB, Maranchie JK, Valente AJ, Mummidi S, and Chandrasekar B. TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells. Biochem Biophys Res Commun 347: 1113–1120, 2006.
211. Pereira S, Zhou M, Mócsai A, and Lowell C. Resting murine neutrophils express functional alpha 4 integrins that signal through Src family kinases. J Immunol 166: 4115–4123, 2001.
212. Pirinccioglu AG, Alyan O, Kizil G, Kangin M, and Beyazit N. Evaluation of oxidative stress in children with congenital heart defects. Pediatr Int 54: 94–98, 2012.
213. Poljsak B, Šuput D, and Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Longev 2013: 956792, 2013.
214. Qin X, Wang X, Wang Y, Tang Z, Cui Q, Xi J, Li YS, Chien S, and Wang N. MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1 expression in human umbilical vein endothelial cells. Proc Natl Acad Sci U S A 107: 3240–3244, 2010.
215. Rafikov R, Dimitropoulou C, Aggarwal S, Kangath A, Gross C, Pardo D, Sharma S, Jezierska-Drutel A, Patel V, Snead C, Lucas R, Verin A, Fulton D, Catravas JD, and Black SM. Lipopolysaccharide-induced lung injury involves the nitration-mediated activation of RhoA. J Biol Chem 289: 4710–4722, 2014.
216. Rafikov R, Rafikova O, Aggarwal S, Gross C, Sun X, Desai J, Fulton D, and Black SM. Asymmetric dimethylarginine induces endothelial nitric-oxide synthase mitochondrial redistribution through the nitration-mediated activation of Akt1. J Biol Chem 288: 6212–6226, 2013.
217. Rapoport RM. Acute nitric oxide synthase inhibition and endothelin-1-dependent arterial pressure elevation. Front Pharmacol 5: 57, 2014.
218. Reddy SP, Hassoun PM, and Brower R. Redox imbalance and ventilator-induced lung injury. Antioxid Redox Signal 9: 2003–2012, 2007.
219. Reiss LK, Uhlig U, and Uhlig S. Models and mechanisms of acute lung injury caused by direct insults. Eur J Cell Biol 91: 590–601, 2012.
220. Reiter G, Reiter U, Kovacs G, Olschewski H, and Fuchsjäger M. Blood flow vortices along the main pulmonary artery measured with MR imaging for diagnosis of pulmonary hypertension. Radiology 275: 71–79, 2015.
221. Rose ML, Strange G, King I, Arnup S, Vidmar S, O'Donnell C, Kermeen F, Grigg L, Weintraub RG, and Celermajer DS. Congenital heart disease-associated pulmonary arterial hypertension: preliminary results from a novel registry. Intern Med J 42: 874–879, 2012.
222. Rossi NF, Black SM, Telemaque-Potts S, and Chen H. Neuronal nitric oxide synthase activity in the paraventricular nucleus buffers central endothelin-1- induced pressor response and vasopressin secretion. J Cardiovasc Pharmacol 44(Suppl. 1): S283–S288, 2004.
223. Ryan J, Dasgupta A, Huston J, Chen KH, and Archer SL. Mitochondrial dynamics in pulmonary arterial hypertension. J Mol Med (Berl) 93: 229–242, 2015.
224. Ryan JJ and Archer SL. Emerging concepts in the molecular basis of pulmonary arterial hypertension: part I: metabolic plasticity and mitochondrial dynamics in the pulmonary circulation and right ventricle in pulmonary arterial hypertension. Circulation 131: 1691–1702, 2015.
225. Ryan JJ, Marsboom G, Fang YH, Toth PT, Morrow E, Luo N, Piao L, Hong Z, Ericson K, Zhang HJ, Han M, Haney CR, Chen CT, Sharp WW, and Archer SL. PGC1alpha-mediated mitofusin-2 deficiency in female rats and humans with pulmonary arterial hypertension. Am J Respir Crit Care Med 187: 865–878, 2013.
226. Saliez J, Bouzin C, Rath G, Ghisdal P, Desjardins F, Rezzani R, Rodella LF, Vriens J, Nilius B, Feron O, Balligand JL, and Dessy C. Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells. Circulation 117: 1065–1074, 2008.
227. Sanders KA and Hoidal JR. The NOX on pulmonary hypertension. Circ Res 101: 224–226, 2007.
228. Sandow SL and Tare M. C-type natriuretic peptide: a new endothelium-derived hyperpolarizing factor? Trends Pharmacol Sci 28: 61–67, 2007.
229. Sandqvist A, Schneede J, Kylhammar D, Henrohn D, Lundgren J, Hedeland M, Bondesson U, Rådegran G, and Wikström G. Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction. Heart Vessels 33: 255–263, 2018.
230. Santel A and Frank S. Shaping mitochondria: the complex posttranslational regulation of the mitochondrial fission protein DRP1. IUBMB Life 60: 448–455, 2008.
231. Sathanoori R, Bryl-Gorecka P, Müller CE, Erb L, Weisman GA, Olde B, and Erlinge D. P2Y2 receptor modulates shear stress-induced cell alignment and actin stress fibers in human umbilical vein endothelial cells. Cell Mol Life Sci 74: 731–746, 2017.
232. Sathanoori R, Rosi F, Gu BJ, Wiley JS, Müller CE, Olde B, and Erlinge D. Shear stress modulates endothelial KLF2 through activation of P2X4. Purinergic Signal 11: 139–153, 2015.
233. Sato K, Kadiiska MB, Ghio AJ, Corbett J, Fann YC, Holland SM, Thurman RG, and Mason RP. In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS. FASEB J 16: 1713–1720, 2002.
234. Scheitlin CG, Nair DM, Crestanello JA, Zweier JL, and Alevriadou BR. Fluid mechanical forces and endothelial mitochondria: a bioengineering perspective. Cell Mol Bioeng 7: 483–496, 2014.
235. Searles CD. Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression. Am J Physiol Cell Physiol 291: C803–C816, 2006.
236. Sharma S, Aramburo A, Rafikov R, Sun X, Kumar S, Oishi PE, Datar SA, Raff G, Xoinis K, Kalkan G, Fratz S, Fineman JR, and Black SM. L-carnitine preserves endothelial function in a lamb model of increased pulmonary blood flow. Pediatr Res 74: 39–47, 2013.
237. Sharma S, Barton J, Rafikov R, Aggarwal S, Kuo HC, Oishi PE, Datar SA, Fineman JR, and Black SM. Chronic inhibition of PPAR-gamma signaling induces endothelial dysfunction in the juvenile lamb. Pulm Pharmacol Ther 26: 271–280, 2013.
238. Sharma S, Smith A, Kumar S, Aggarwal S, Rehmani I, Snead C, Harmon C, Fineman J, Fulton D, Catravas JD, and Black SM. Mechanisms of nitric oxide synthase uncoupling in endotoxin-induced acute lung injury: role of asymmetric dimethylarginine. Vascul Pharmacol 52: 182–190, 2010.
239. Sharma S, Sud N, Wiseman DA, Carter AL, Kumar S, Hou Y, Rau T, Wilham J, Harmon C, Oishi P, Fineman JR, and Black SM. Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 294: L46–L56, 2008.
240. Sharma S, Sun X, Rafikov R, Kumar S, Hou Y, Oishi PE, Datar SA, Raff G, Fineman JR, and Black SM. PPAR-gamma regulates carnitine homeostasis and mitochondrial function in a lamb model of increased pulmonary blood flow. PLoS One 7: e41555, 2012.
241. Shi-Wen X, Chen Y, Denton CP, Eastwood M, Renzoni EA, Bou-Gharios G, Pearson JD, Dashwood M, du Bois RM, Black CM, Leask A, and Abraham DJ. Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol Biol Cell 15: 2707–2719, 2004.
242. Shikata Y, Rios A, Kawkitinarong K, DePaola N, Garcia JG, and Birukov KG. Differential effects of shear stress and cyclic stretch on focal adhesion remodeling, site-specific FAK phosphorylation, and small GTPases in human lung endothelial cells. Exp Cell Res 304: 40–49, 2005.
243. Shimokawa H. Hydrogen peroxide as an endothelium-derived hyperpolarizing factor. Pflugers Arch 459: 915–922, 2010.
244. Shimokawa H and Godo S. Diverse functions of endothelial NO synthases system: NO and EDH. J Cardiovasc Pharmacol 67: 361–366, 2016.
245. Shimokawa H and Morikawa K. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in animals and humans. J Mol Cell Cardiol 39: 725–732, 2005.
246. Silber HA, Bluemke DA, Ouyang P, Du YP, Post WS, and Lima JA. The relationship between vascular wall shear stress and flow-mediated dilation: endothelial function assessed by phase-contrast magnetic resonance angiography. J Am Coll Cardiol 38: 1859–1865, 2001.
247. Siu KL, Gao L, and Cai H. Differential roles of protein complexes NOX1-NOXO1 and NOX2-p47phox in mediating endothelial redox responses to oscillatory and unidirectional laminar shear stress. J Biol Chem 291: 8653–8662, 2016.
248. Stankevicius E, Kevelaitis E, Vainorius E, and Simonsen U. Role of nitric oxide and other endothelium-derived factors [in Lithuanian]. Medicina (Kaunas) 39: 333–341, 2003.
249. Steele PM, Fuster V, Cohen M, Ritter DG, and McGoon DC. Isolated atrial septal defect with pulmonary vascular obstructive disease—long-term follow-up and prediction of outcome after surgical correction. Circulation 76: 1037–1042, 1987.
250. Stirpe F and Della Corte E. The regulation of rat liver xanthine oxidase. Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J Biol Chem 244: 3855–3863, 1969.
251. Sturrock A, Cahill B, Norman K, Huecksteadt TP, Hill K, Sanders K, Karwande SV, Stringham JC, Bull DA, Gleich M, Kennedy TP, and Hoidal JR. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 290: L661–L673, 2006.
252. Suárez Y, Fernández-Hernando C, Pober JS, and Sessa WC. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res 100: 1164–1173, 2007.
253. Sud N and Black SM. Endothelin-1 impairs nitric oxide signaling in endothelial cells through a protein kinase Cdelta-dependent activation of STAT3 and decreased endothelial nitric oxide synthase expression. DNA Cell Biol 28: 543–553, 2009.
254. Sun X, Fratz S, Sharma S, Hou Y, Rafikov R, Kumar S, Rehmani I, Tian J, Smith A, Schreiber C, Reiser J, Naumann S, Haag S, Hess J, Catravas JD, Patterson C, Fineman JR, and Black SM. C-terminus of heat shock protein 70-interacting protein-dependent GTP cyclohydrolase I degradation in lambs with increased pulmonary blood flow. Am J Respir Cell Mol Biol 45: 163–171, 2011.
255. Sun X, Kumar S, Sharma S, Aggarwal S, Lu Q, Gross C, Rafikova O, Lee SG, Dasarathy S, Hou Y, Meadows ML, Han W, Su Y, Fineman JR, and Black SM. Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase. Am J Respir Cell Mol Biol 50: 1084–1095, 2014.
256. Sun X, Sharma S, Fratz S, Kumar S, Rafikov R, Aggarwal S, Rafikova O, Lu Q, Burns T, Dasarathy S, Wright J, Schreiber C, Radman M, Fineman JR, and Black SM. Disruption of endothelial cell mitochondrial bioenergetics in lambs with increased pulmonary blood flow. Antioxid Redox Signal 18: 1739–1752, 2013.
257. Suzuki M, Naruse K, Asano Y, Okamoto T, Nishikimi N, Sakurai T, Nimura Y, and Sokabe M. Up-regulation of integrin beta 3 expression by cyclic stretch in human umbilical endothelial cells. Biochem Biophys Res Commun 239: 372–376, 1997.
258. Syrkina O, Jafari B, Hales CA, and Quinn DA. Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury. Respirology 13: 333–340, 2008.
259. Szulcek R, Happé CM, Rol N, Fontijn RD, Dickhoff C, Hartemink KJ, Grünberg K, Tu L, Timens W, Nossent GD, Paul MA, Leyen TA, Horrevoets AJ, de Man FS, Guignabert C, Yu PB, Vonk-Noordegraaf A, van Nieuw Amerongen GP, and Bogaard HJ. Delayed microvascular shear adaptation in pulmonary arterial hypertension. Role of platelet endothelial cell adhesion molecule-1 cleavage. Am J Respir Crit Care Med 193: 1410–1420, 2016.
260. Takabe W, Jen N, Ai L, Hamilton R, Wang S, Holmes K, Dharbandi F, Khalsa B, Bressler S, Barr ML, Li R, and Hsiai TK. Oscillatory shear stress induces mitochondrial superoxide production: implication of NADPH oxidase and c-Jun NH2-terminal kinase signaling. Antioxid Redox Signal 15: 1379–1388, 2011.
261. Takac I, Schröder K, and Brandes RP. The Nox family of NADPH oxidases: friend or foe of the vascular system? Curr Hypertens Rep 14: 70–78, 2012.
262. Tanaka KA, Key NS, and Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg 108: 1433–1446, 2009.
263. Tanaka Y, Yamaki F, Koike K, and Toro L. New insights into the intracellular mechanisms by which PGI2 analogues elicit vascular relaxation: cyclic AMP-independent, Gs-protein mediated-activation of MaxiK channel. Curr Med Chem Cardiovasc Hematol Agents 2: 257–265, 2004.
264. Tang H, Babicheva A, McDermott KM, Gu Y, Ayon RJ, Song S, Wang Z, Gupta A, Zhou T, Sun X, Dash S, Wang Z, Balistrieri A, Zheng Q, Cordery AG, Desai AA, Rischard F, Khalpey Z, Wang J, Black SM, Garcia JGN, Makino A, and Yuan JX. Endothelial HIF-2alpha contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition. Am J Physiol Lung Cell Mol Physiol 314: L256–L275, 2018.
265. Taylor SG and Weston AH. Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci 9: 272–274, 1988.
266. Tesfamariam B. Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med 16: 383–391, 1994.
267. Tirone F, Radu L, Craescu CT, and Cox JA. Identification of the binding site for the regulatory calcium-binding domain in the catalytic domain of NOX5. Biochemistry 49: 761–771, 2010.
268. Touyz RM, Yao G, Quinn MT, Pagano PJ, and Schiffrin EL. p47phox associates with the cytoskeleton through cortactin in human vascular smooth muscle cells: role in NAD(P)H oxidase regulation by angiotensin II. Arterioscler Thromb Vasc Biol 25: 512–518, 2005.
269. Tran QK, Ohashi K, and Watanabe H. Calcium signalling in endothelial cells. Cardiovasc Res 48: 13–22, 2000.
270. Tsushima K, King LS, Aggarwal NR, De Gorordo A, D'Alessio FR, and Kubo K. Acute lung injury review. Intern Med 48: 621–630, 2009.
271. Tugues S, Honjo S, König C, Padhan N, Kroon J, Gualandi L, Li X, Barkefors I, Thijssen VL, Griffioen AW, and Claesson-Welsh L. Tetraspanin CD63 promotes vascular endothelial growth factor receptor 2-beta1 integrin complex formation, thereby regulating activation and downstream signaling in endothelial cells in vitro and in vivo. J Biol Chem 288: 19060–19071, 2013.
272. Umanskiy K, Robinson C, Cave C, Williams MA, Lentsch AB, Cuschieri J, and Solomkin JS. NADPH oxidase activation in fibronectin adherent human neutrophils: a potential role for beta1 integrin ligation. Surgery 134: 378–383, 2003.
273. van der Vliet A, Janssen-Heininger YMW, and Anathy V. Oxidative stress in chronic lung disease: from mitochondrial dysfunction to dysregulated redox signaling. Mol Aspects Med 63: 59–69, 2018.
274. Van Hung T, Emoto N, Vignon-Zellweger N, Nakayama K, Yagi K, Suzuki Y, and Hirata K. Inhibition of vascular endothelial growth factor receptor under hypoxia causes severe, human-like pulmonary arterial hypertension in mice: potential roles of interleukin-6 and endothelin. Life Sci 118: 313–328, 2014.
275. Vandenbroucke E, Mehta D, Minshall R, and Malik AB. Regulation of endothelial junctional permeability. Ann N Y Acad Sci 1123: 134–145, 2008.
276. Vaporidi K, Francis RC, Bloch KD, and Zapol WM. Nitric oxide synthase 3 contributes to ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 299: L150–L159, 2010.
277. Ventura-Clapier R, Garnier A, and Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 79: 208–217, 2008.
278. Verónica Donoso M, Hernández F, Villalón T, Acuña-Castillo C, and Pablo Huidobro-Toro J. Pharmacological dissection of the cellular mechanisms associated to the spontaneous and the mechanically stimulated ATP release by mesentery endothelial cells: roles of thrombin and TRPV. Purinergic Signal 14: 121–139, 2018.
279. Viñas JL, Burger D, Zimpelmann J, Haneef R, Knoll W, Campbell P, Gutsol A, Carter A, Allan DS, and Burns KD. Transfer of microRNA-486-5p from human endothelial colony forming cell-derived exosomes reduces ischemic kidney injury. Kidney Int 90: 1238–1250, 2016.
280. Vitali SH, Hansmann G, Rose C, Fernandez-Gonzalez A, Scheid A, Mitsialis SA, and Kourembanas S. The Sugen 5416/hypoxia mouse model of pulmonary hypertension revisited: long-term follow-up. Pulm Circ 4: 619–629, 2015.
281. Wallace CS and Truskey GA. Direct-contact co-culture between smooth muscle and endothelial cells inhibits TNF-alpha-mediated endothelial cell activation. Am J Physiol Heart Circ Physiol 299: H338–H346, 2010.
282. Wang HW, Huang BS, White RA, Chen A, Ahmad M, and Leenen FH. Mineralocorticoid and angiotensin II type 1 receptors in the subfornical organ mediate angiotensin II - induced hypothalamic reactive oxygen species and hypertension. Neuroscience 329: 112–121, 2016.
283. Wang KC, Garmire LX, Young A, Nguyen P, Trinh A, Subramaniam S, Wang N, Shyy JY, Li YS, and Chien S. Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth. Proc Natl Acad Sci U S A 107: 3234–3239, 2010.
284. Wang T, Gross C, Desai AA, Zemskov E, Wu X, Garcia AN, Jacobson JR, Yuan JX, Garcia JG, and Black SM. Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets. Am J Physiol Lung Cell Mol Physiol 312: L452–L476, 2017.
285. Wang Z and Chesler NC. Pulmonary vascular wall stiffness: an important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulm Circ 1: 212–223, 2011.
286. Waud WR and Rajagopalan KV. Purification and properties of the NAD+-dependent (type D) and O2-dependent (type O) forms of rat liver xanthine dehydrogenase. Arch Biochem Biophys 172: 354–364, 1976.
287. Wedgwood S and Black SM. Endothelin-1 decreases endothelial NOS expression and activity through ETA receptor-mediated generation of hydrogen peroxide. Am J Physiol Lung Cell Mol Physiol 288: L480–L487, 2005.
288. Wedgwood S, Lakshminrusimha S, Schumacker PT, and Steinhorn RH. Cyclic stretch stimulates mitochondrial reactive oxygen species and Nox4 signaling in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 309: L196–L203, 2015.
289. White SJ, Hayes EM, Lehoux S, Jeremy JY, Horrevoets AJ, and Newby AC. Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress. J Cell Physiol 226: 2841–2848, 2011.
290. Williams DA, Zheng Y, and Cancelas JA. Rho GTPases and regulation of hematopoietic stem cell localization. Methods Enzymol 439: 365–393, 2008.
291. Wolfson RK, Mapes B, and Garcia JGN. Excessive mechanical stress increases HMGB1 expression in human lung microvascular endothelial cells via STAT3. Microvasc Res 92: 50–55, 2014.
292. Wu F, Szczepaniak WS, Shiva S, Liu H, Wang Y, Wang L, Wang Y, Kelley EE, Chen AF, Gladwin MT, and McVerry BJ. Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled superoxide production and endothelial barrier dysfunction in acute lung injury. Am J Physiol Lung Cell Mol Physiol 307: L987–L997, 2014.
293. Wu LH, Chang HC, Ting PC, and Wang DL. Laminar shear stress promotes mitochondrial homeostasis in endothelial cells. J Cell Physiol 233: 5058–5069, 2018.
294. Wu W, Xiao H, Laguna-Fernandez A, Villarreal G Jr., Wang KC, Geary GG, Zhang Y, Wang WC, Huang HD, Zhou J, Li YS, Chien S, Garcia-Cardena G, and Shyy JY. Flow-dependent regulation of Kruppel-like factor 2 is mediated by microRNA-92a. Circulation 124: 633–641, 2011.
295. Xu W, Kaneko FT, Zheng S, Comhair SA, Janocha AJ, Goggans T, Thunnissen FB, Farver C, Hazen SL, Jennings C, Dweik RA, Arroliga AC, and Erzurum SC. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 18: 1746–1748, 2004.
296. Xu Y, Fang F, Zhang J, Josson S, St Clair WH, and St Clair DK. miR-17* suppresses tumorigenicity of prostate cancer by inhibiting mitochondrial antioxidant enzymes. PLoS One 5: e14356, 2010.
297. Yamamoto K, Korenaga R, Kamiya A, and Ando J. Fluid shear stress activates Ca(2+) influx into human endothelial cells via P2X4 purinoceptors. Circ Res 87: 385–391, 2000.
298. Yamamoto K, Sokabe T, Ohura N, Nakatsuka H, Kamiya A, and Ando J. Endogenously released ATP mediates shear stress-induced Ca2+ influx into pulmonary artery endothelial cells. Am J Physiol Heart Circ Physiol 285: H793–H803, 2003.
299. Yan SR, Fumagalli L, Dusi S, and Berton G. Tumor necrosis factor triggers redistribution to a Triton X-100-insoluble, cytoskeletal fraction of beta 2 integrins, NADPH oxidase components, tyrosine phosphorylated proteins, and the protein tyrosine kinase p58fgr in human neutrophils adherent to fibrinogen. J Leukoc Biol 58: 595–606, 1995.
300. Yang YM, Huang A, Kaley G, and Sun D. eNOS uncoupling and endothelial dysfunction in aged vessels. Am J Physiol Heart Circ Physiol 297: H1829–H1836, 2009.
301. Yokota T, Shiraishi R, Aida T, Iwai K, Liu NM, Yokoyama U, and Minamisawa S. Thromboxane A(2) receptor stimulation promotes closure of the rat ductus arteriosus through enhancing neointima formation. PLoS One 9: e94895, 2014.
302. Zhang B, Niu W, Dong HY, Liu ML, Luo Y, and Li ZC. Hypoxia induces endothelial-mesenchymal transition in pulmonary vascular remodeling. Int J Mol Med 42: 270–278, 2018.
303. Zhang S, Yang T, Xu X, Wang M, Zhong L, Yang Y, Zhai Z, Xiao F, and Wang C. Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study. BMC Pulm Med 15: 50, 2015.
304. Zhang X, Ng WL, Wang P, Tian L, Werner E, Wang H, Doetsch P, and Wang Y. MicroRNA-21 modulates the levels of reactive oxygen species by targeting SOD3 and TNFalpha. Cancer Res 72: 4707–4713, 2012.
305. Zhang X, Zhang T, Gao F, Li Q, Shen C, Li Y, Li W, and Zhang X. Fasudil, a Rho-kinase inhibitor, prevents intimamedia thickening in a partially ligated carotid artery mouse model: effects of fasudil in flowinduced vascular remodeling. Mol Med Rep 12: 7317–7325, 2015.
306. Zhao YY, Zhao YD, Mirza MK, Huang JH, Potula HH, Vogel SM, Brovkovych V, Yuan JX, Wharton J, and Malik AB. Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration. J Clin Invest 119: 2009–2018, 2009.
307. Zheng J, Zhang K, Wang Y, Cao J, Zhang F, Zhou Q, and Dong R. Identification of a microRNA signature in endothelial cells with mechanical stretch stimulation. Mol Med Rep 12: 3525–3530, 2015.
308. Zhou C, Huang J, Chen J, Lai J, Zhu F, Xu X, and Wang DW. CYP2J2-derived EETs attenuated angiotensin II-induced adventitial remodeling via reduced inflammatory response. Cell Physiol Biochem 39: 721–739, 2016.
309. Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ, Li JY, and Chien S. MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci U S A 108: 10355–10360, 2011.
310. Zhu H, Itoh K, Yamamoto M, Zweier JL, and Li Y. Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury. FEBS Lett 579: 3029–3036, 2005.
311. Zhu H, Jia Z, Zhang L, Yamamoto M, Misra HP, Trush MA, and Li Y. Antioxidants and phase 2 enzymes in macrophages: regulation by Nrf2 signaling and protection against oxidative and electrophilic stress. Exp Biol Med (Maywood) 233: 463–474, 2008.
312. Zhu X, Gao Q, Tu Q, Zhong Y, Zhu D, Mao C, and Xu Z. Prenatal hypoxia enhanced angiotensin II-mediated vasoconstriction via increased oxidative signaling in fetal rats. Reprod Toxicol 60: 21–28, 2016.
313. Zhuang D, Ceacareanu AC, Lin Y, Ceacareanu B, Dixit M, Chapman KE, Waters CM, Rao GN, and Hassid A. Nitric oxide attenuates insulin- or IGF-I-stimulated aortic smooth muscle cell motility by decreasing H2O2 levels: essential role of cGMP. Am J Physiol Heart Circ Physiol 286: H2103–H2112, 2004.
314. Zou MH, Klein T, Pasquet JP, and Ullrich V. Interleukin 1beta decreases prostacyclin synthase activity in rat mesangial cells via endogenous peroxynitrite formation. Biochem J 336: 507–512, 1998.
Information & Authors
Information
Published In
Antioxidants & Redox Signaling
Volume 31 • Issue Number 12 • October 20, 2019
Pages: 819 - 842
PubMed: 30623676
Copyright
Copyright 2019, Mary Ann Liebert, Inc., publishers.
History
Published in print: October 20, 2019
Published online: 11 September 2019
Published ahead of print: 19 March 2019
Published ahead of production: 9 January 2019
Accepted: 3 January 2019
Received: 27 December 2018
Topics
Authors
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Get Access
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.