<iframe src="//www.googletagmanager.com/ns.html?id=GTM-5TSRKG" height="0" width="0" style="display: none; visibility: hidden">
Research Article
No access
Published Online: 21 February 2012

Tumor Necrosis Factor-Alpha and Receptor Activator of Nuclear Factor-κB Ligand Augment Human Macrophage Foam-Cell Destruction of Extracellular Matrix Through Protease-Mediated Processes

Publication: ASSAY and Drug Development Technologies
Volume 10, Issue Number 1

Abstract

By secreting proteases such as cathepsins and matrix metalloproteinases (MMPs), macrophage foam cells may be a major cause of ruptured atherosclerotic plaques. The aims of the present study were to investigate in vitro role of human macrophage foam cells in degrading type I collagen, a major component of extracellular matrix (ECM) in plaques, and to establish whether the pro-inflammatory molecules, tumor necrosis factor (TNF)-alpha, and receptor activator of nuclear factor-κB ligand (RANK-L) increase this degradation. CD14+ monocytes isolated from peripheral blood were differentiated into macrophage foam cells and cultured on a type I collagen matrix in the presence of TNF-alpha and RANK-L. Matrix degradation was measured by the cathepsin K-generated C-terminal cross-linked telopeptide of type I collagen (CTX-I) and the MMP-generated carboxyterminal telopeptide of type I collagen (ICTP) in supernatants showing that macrophage foam cells secrete MMPs and cathepsin K, resulting in release of ICTP and CTX-I. Stimulation with TNF-alpha increased CTX-I and ICTP dose dependently, with ICTP levels increasing by 59% and CTX-I levels increasing by 43%. RANK-L enhanced the release of CTX-I and ICTP by 56% and 72%, respectively. This is, to our knowledge, the first data describing a simple in vitro system in which macrophage foam cells degradation of matrix proteins can be monitored. This degradation can be enhanced by cytokines since TNF-alpha and RANK-L significantly increased the matrix degradation. This in vitro system in part is a model system for the macrophage-mediated proteolytic degradation of the ECM, which is found in many diseases with an inflammatory component.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
De Backer GAmbrosioni EBorch-Johnsen KBrotons CCifkova RDallongeville JEbrahim SFaergeman OGraham IMancia GCats VMOrth-Gomer KPerk JPyorala KRodicio JLSans SSansoy VSechtem USilber SThomsen TWood D. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts)Atherosclerosis2004173381-391. 1. De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Cats VM, Orth-Gomer K, Perk J, Pyorala K, Rodicio JL, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D: European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts). Atherosclerosis 2004;173:381–391.
2.
Skjot-Arkil HBarascuk NRegister TKarsdal MA. Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes: a potential new class of biochemical markersAssay Drug Dev Technol20108542-552. 2. Skjot-Arkil H, Barascuk N, Register T, Karsdal MA: Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes: a potential new class of biochemical markers. Assay Drug Dev Technol 2010;8:542–552.
3.
Lepidi SKenagy RDRaines EWChiu ESChait ARoss RClowes AW. MMP9 production by human monocyte-derived macrophages is decreased on polymerized type I collagenJ Vasc Surg2001341111-1118. 3. Lepidi S, Kenagy RD, Raines EW, Chiu ES, Chait A, Ross R, Clowes AW: MMP9 production by human monocyte-derived macrophages is decreased on polymerized type I collagen. J Vasc Surg 2001;34:1111–1118.
4.
Brauer PR. MMPs—role in cardiovascular development and diseaseFront Biosci200611447-478. 4. Brauer PR: MMPs—role in cardiovascular development and disease. Front Biosci 2006;11:447–478.
5.
Loscalzo JMolecular Mechanismes of AtherosclerosisTaylor & FrancisLondon2000. 5. Loscalzo J: Molecular Mechanismes of Atherosclerosis. Taylor & Francis, London, 2000.
6.
Choudhury RPLee JMGreaves DR. Mechanisms of disease: macrophage-derived foam cells emerging as therapeutic targets in atherosclerosisNat Clin Pract Cardiovasc Med20052309-315. 6. Choudhury RP, Lee JM, Greaves DR: Mechanisms of disease: macrophage-derived foam cells emerging as therapeutic targets in atherosclerosis. Nat Clin Pract Cardiovasc Med 2005;2:309–315.
7.
Takahashi KTakeya MSakashita N. Multifunctional roles of macrophages in the development and progression of atherosclerosis in humans and experimental animalsMed Electron Microsc200235179-203. 7. Takahashi K, Takeya M, Sakashita N: Multifunctional roles of macrophages in the development and progression of atherosclerosis in humans and experimental animals. Med Electron Microsc 2002;35:179–203.
8.
Bobryshev YV. Calcification of elastic fibers in human atherosclerotic plaqueAtherosclerosis2005180293-303. 8. Bobryshev YV: Calcification of elastic fibers in human atherosclerotic plaque. Atherosclerosis 2005;180:293–303.
9.
Rouis M. Matrix metalloproteinases: a potential therapeutic target in atherosclerosisCurr Drug Targets Cardiovasc Haematol Disord20055541-548. 9. Rouis M: Matrix metalloproteinases: a potential therapeutic target in atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:541–548.
10.
Bode MKMosorin MSatta JRisteli LJuvonen TRisteli J. Complete processing of type III collagen in atherosclerotic plaquesArterioscler Thromb Vasc Biol1999191506-1511. 10. Bode MK, Mosorin M, Satta J, Risteli L, Juvonen T, Risteli J: Complete processing of type III collagen in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 1999;19:1506–1511.
11.
Rekhter MD. Collagen synthesis in atherosclerosis: too much and not enoughCardiovasc Res199941376-384. 11. Rekhter MD: Collagen synthesis in atherosclerosis: too much and not enough. Cardiovasc Res 1999;41:376–384.
12.
Eriksen HASatta JRisteli JVeijola MVare PSoini Y. Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosisAtherosclerosis200618991-98. 12. Eriksen HA, Satta J, Risteli J, Veijola M, Vare P, Soini Y: Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosis. Atherosclerosis 2006;189:91–98.
13.
Barnes MJFarndale RW. Collagens and atherosclerosisExp Gerontol199934513-525. 13. Barnes MJ, Farndale RW: Collagens and atherosclerosis. Exp Gerontol 1999;34:513–525.
14.
Katsuda SKaji T. Atherosclerosis and extracellular matrixJ Atheroscler Thromb200310267-274. 14. Katsuda S, Kaji T: Atherosclerosis and extracellular matrix. J Atheroscler Thromb 2003;10:267–274.
15.
Lipinski MJFrias JCFayad ZA. Advances in detection and characterization of atherosclerosis using contrast agents targeting the macrophageJ Nucl Cardiol200613699-709. 15. Lipinski MJ, Frias JC, Fayad ZA: Advances in detection and characterization of atherosclerosis using contrast agents targeting the macrophage. J Nucl Cardiol 2006;13:699–709.
16.
Moreno PRFalk EPalacios IFNewell JBFuster VFallon JT. Macrophage infiltration in acute coronary syndromesImplications for plaque rupture. Circulation199490775-778. 16. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT: Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 1994;90:775–778.
17.
van der Wal ACBecker AEvan der Loos CMTigges AJDas PK. Fibrous and lipid-rich atherosclerotic plaques are part of interchangeable morphologies related to inflammation: a conceptCoron Artery Dis19945463-469. 17. van der Wal AC, Becker AE, van der Loos CM, Tigges AJ, Das PK: Fibrous and lipid-rich atherosclerotic plaques are part of interchangeable morphologies related to inflammation: a concept. Coron Artery Dis 1994;5:463–469.
18.
Kuzuya MNakamura KSasaki TCheng XWItohara SIguchi A. Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient miceArterioscler Thromb Vasc Biol2006261120-1125. 18. Kuzuya M, Nakamura K, Sasaki T, Cheng XW, Itohara S, Iguchi A: Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice. Arterioscler Thromb Vasc Biol 2006;26:1120–1125.
19.
Gough PJGomez IGWille PTRaines EW. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient miceJ Clin Invest200611659-69. 19. Gough PJ, Gomez IG, Wille PT, Raines EW: Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest 2006;116:59–69.
20.
Kuzuya MNakamura KSasaki TCheng XWItohara SIguchi A. Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient miceArterioscler Thromb Vasc Biol2006261120-1125. 20. Kuzuya M, Nakamura K, Sasaki T, Cheng XW, Itohara S, Iguchi A: Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice. Arterioscler Thromb Vasc Biol 2006;26:1120–1125.
21.
Luttun ALutgens EManderveld AMaris KCollen DCarmeliet PMoons L. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growthCirculation20041091408-1414. 21. Luttun A, Lutgens E, Manderveld A, Maris K, Collen D, Carmeliet P, Moons L: Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Circulation 2004;109:1408–1414.
22.
Sundstrom JVasan RS. Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic eventsCurr Opin Lipidol20061745-53. 22. Sundstrom J, Vasan RS: Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events. Curr Opin Lipidol 2006;17:45–53.
23.
Rouis MAdamy CDuverger NLesnik PHorellou PMoreau MEmmanuel FCaillaud JMLaplaud PMDachet CChapman MJ. Adenovirus-mediated over-expression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient miceCirculation1999100533-540. 23. Rouis M, Adamy C, Duverger N, Lesnik P, Horellou P, Moreau M, Emmanuel F, Caillaud JM, Laplaud PM, Dachet C, Chapman MJ: Adenovirus-mediated over-expression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice. Circulation 1999;100:533–540.
24.
Allaire EForough RClowes MStarcher BClowes AW. Local over-expression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat modelJ Clin Invest19981021413-1420. 24. Allaire E, Forough R, Clowes M, Starcher B, Clowes AW: Local over-expression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model. J Clin Invest 1998;102:1413–1420.
25.
Garcia-Touchard AHenry TDSangiorgi GSpagnoli LGMauriello AConover CSchwartz RS. Extracellular proteases in atherosclerosis and restenosisArterioscler Thromb Vasc Biol2005251119-1127. 25. Garcia-Touchard A, Henry TD, Sangiorgi G, Spagnoli LG, Mauriello A, Conover C, Schwartz RS: Extracellular proteases in atherosclerosis and restenosis. Arterioscler Thromb Vasc Biol 2005;25:1119–1127.
26.
Lutgens ELutgens SPFaber BCHeeneman SGijbels MMde Winther MPFrederik Pvan dM IDaugherty ASijbers AMFisher ALong CJSaftig PBlack DDaemen MJCleutjens KB. Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formationCirculation200611398-107. 26. Lutgens E, Lutgens SP, Faber BC, Heeneman S, Gijbels MM, de Winther MP, Frederik P, van dM, I, Daugherty A, Sijbers AM, Fisher A, Long CJ, Saftig P, Black D, Daemen MJ, Cleutjens KB: Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation 2006;113:98–107.
27.
Lutgens SPCleutjens KBDaemen MJHeeneman S. Cathepsin cysteine proteases in cardiovascular diseaseFASEB J2007213029-3041. 27. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S: Cathepsin cysteine proteases in cardiovascular disease. FASEB J 2007;21:3029–3041.
28.
Sukhova GKZhang YPan JHWada YYamamoto TNaito MKodama TTsimikas SWitztum JLLu MLSakara YChin MTLibby PShi GP. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient miceJ Clin Invest2003111897-906. 28. Sukhova GK, Zhang Y, Pan JH, Wada Y, Yamamoto T, Naito M, Kodama T, Tsimikas S, Witztum JL, Lu ML, Sakara Y, Chin MT, Libby P, Shi GP: Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest 2003;111:897–906.
29.
Jaffer FAKim DEQuinti LTung CHAikawa EPande ANKohler RHShi GPLibby PWeissleder R. Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensorCirculation20071152292-2298. 29. Jaffer FA, Kim DE, Quinti L, Tung CH, Aikawa E, Pande AN, Kohler RH, Shi GP, Libby P, Weissleder R: Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation 2007;115:2292–2298.
30.
Abdul-Hussien HSoekhoe RGWeber Eder Thusen JHKleemann RMulder Avan Bockel JHHanemaaijer RLindeman JH. Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenasesAm J Pathol2007170809-817. 30. Abdul-Hussien H, Soekhoe RG, Weber E, der Thusen JH, Kleemann R, Mulder A, van Bockel JH, Hanemaaijer R, Lindeman JH: Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases. Am J Pathol 2007;170:809–817.
31.
Chapman HARiese RJShi GP. Emerging roles for cysteine proteases in human biologyAnnu Rev Physiol19975963-88. 31. Chapman HA, Riese RJ, Shi GP: Emerging roles for cysteine proteases in human biology. Annu Rev Physiol 1997;59:63–88.
32.
Buhling FReisenauer AGerber AKruger SWeber EBromme DRoessner AAnsorge SWelte TRocken C. Cathepsin K—a marker of macrophage differentiation?J Pathol2001195375-382. 32. Buhling F, Reisenauer A, Gerber A, Kruger S, Weber E, Bromme D, Roessner A, Ansorge S, Welte T, Rocken C: Cathepsin K—a marker of macrophage differentiation? J Pathol 2001;195:375–382.
33.
Hakala JKOksjoki RLaine PDu HGrabowski GAKovanen PTPentikainen MO. Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extra-cellularly in human atherosclerotic lesionsArterioscler Thromb Vasc Biol2003231430-1436. 33. Hakala JK, Oksjoki R, Laine P, Du H, Grabowski GA, Kovanen PT, Pentikainen MO: Lysosomal enzymes are released from cultured human macrophages, hydrolyze LDL in vitro, and are present extra-cellularly in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2003;23:1430–1436.
34.
Karsdal MAHjorth PHenriksen KKirkegaard TNielsen KLLou HDelaisse JMFoged NT. Transforming growth factor-beta controls human osteoclastogenesis through the p38 MAPK and regulation of RANK expressionJ Biol Chem200327844975-44987. 34. Karsdal MA, Hjorth P, Henriksen K, Kirkegaard T, Nielsen KL, Lou H, Delaisse JM, Foged NT: Transforming growth factor-beta controls human osteoclastogenesis through the p38 MAPK and regulation of RANK expression. J Biol Chem 2003;278:44975–44987.
35.
Sorensen MGHenriksen KSchaller SHenriksen DBNielsen FCDziegiel MHKarsdal MA. Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral bloodJ Bone Miner Metab20072536-45. 35. Sorensen MG, Henriksen K, Schaller S, Henriksen DB, Nielsen FC, Dziegiel MH, Karsdal MA: Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood. J Bone Miner Metab 2007;25:36–45.
36.
Samokhin AOWong ASaftig PBromme D. Role of cathepsin K in structural changes in brachiocephalic artery during progression of atherosclerosis in apoE-deficient miceAtherosclerosis200820058-68. 36. Samokhin AO, Wong A, Saftig P, Bromme D: Role of cathepsin K in structural changes in brachiocephalic artery during progression of atherosclerosis in apoE-deficient mice. Atherosclerosis 2008;200:58–68.
37.
Sassi MLEriksen HRisteli LNiemi SMansell JGowen MRisteli J. Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin KBone200026367-373. 37. Sassi ML, Eriksen H, Risteli L, Niemi S, Mansell J, Gowen M, Risteli J: Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K. Bone 2000;26:367–373.
38.
Garnero PFerreras MKarsdal MANicamhlaoibh RRisteli JBorel OQvist PDelmas PDFoged NTDelaisse JM. The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradationJ Bone Miner Res200318859-867. 38. Garnero P, Ferreras M, Karsdal MA, Nicamhlaoibh R, Risteli J, Borel O, Qvist P, Delmas PD, Foged NT, Delaisse JM: The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res 2003;18:859–867.
39.
Zhang LPeppel KSivashanmugam POrman ESBrian LExum STFreedman NJ. Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosisArterioscler Thromb Vasc Biol2007271087-1094. 39. Zhang L, Peppel K, Sivashanmugam P, Orman ES, Brian L, Exum ST, Freedman NJ: Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27:1087–1094.
40.
Ridker PMRifai NPfeffer MSacks FLepage SBraunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarctionCirculation20001012149-2153. 40. Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E: Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101:2149–2153.
41.
Branen LHovgaard LNitulescu MBengtsson ENilsson JJovinge S. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout miceArterioscler Thromb Vasc Biol2004242137-2142. 41. Branen L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S: Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2004;24:2137–2142.
42.
Galis ZSMuszynski MSukhova GKSimon-Morrissey ELibby P. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesionsAnn NY Acad Sci1995748501-507. 42. Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P: Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann NY Acad Sci 1995;748:501–507.
43.
Rajavashisth TBXu XPJovinge SMeisel SXu XOChai NNFishbein MCKaul SCercek BSharifi BShah PK. Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediatorsCirculation1999993103-3109. 43. Rajavashisth TB, Xu XP, Jovinge S, Meisel S, Xu XO, Chai NN, Fishbein MC, Kaul S, Cercek B, Sharifi B, Shah PK: Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediators. Circulation 1999;99:3103–3109.
44.
Barath PFishbein MCCao JBerenson JHelfant RHForrester JS. Detection and localization of tumor necrosis factor in human atheromaAm J Cardiol199065297-302. 44. Barath P, Fishbein MC, Cao J, Berenson J, Helfant RH, Forrester JS: Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol 1990;65:297–302.
45.
Tipping PGHancock WW. Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaquesAm J Pathol19931421721-1728. 45. Tipping PG, Hancock WW: Production of tumor necrosis factor and interleukin-1 by macrophages from human atheromatous plaques. Am J Pathol 1993;142:1721–1728.
46.
Cugno MIngegnoli FGualtierotti RFantini F. Potential effect of anti-tumour necrosis factor-alpha treatment on reducing the cardiovascular risk related to rheumatoid arthritisCurr Vasc Pharmacol20108285-292. 46. Cugno M, Ingegnoli F, Gualtierotti R, Fantini F: Potential effect of anti-tumour necrosis factor-alpha treatment on reducing the cardiovascular risk related to rheumatoid arthritis. Curr Vasc Pharmacol 2010;8:285–292.
47.
Jacobsson LTTuresson CGulfe AKapetanovic MCPetersson IFSaxne TGeborek P. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritisJ Rheumatol2005321213-1218. 47. Jacobsson LT, Turesson C, Gulfe A, Kapetanovic MC, Petersson IF, Saxne T, Geborek P: Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005;32:1213–1218.
48.
Schwarz EMRitchlin CT. Clinical development of anti-RANKL therapyArthritis Res Ther20079Suppl 1S7. 48. Schwarz EM, Ritchlin CT: Clinical development of anti-RANKL therapy. Arthritis Res Ther 2007;9(Suppl 1):S7.
49.
Venuraju SMYerramasu ACorder RLahiri A. Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidityJ Am Coll Cardiol2010552049-2061. 49. Venuraju SM, Yerramasu A, Corder R, Lahiri A: Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol 2010;55:2049–2061.
50.
D'Amelio PIsaia GIsaia GC. The osteoprotegerin/RANK/RANKL system: a bone key to vascular diseaseJ Endocrinol Invest2009324 Suppl6-9. 50. D'Amelio P, Isaia G, Isaia GC: The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease. J Endocrinol Invest 2009;32(4 Suppl):6–9.
51.
Kim JMin JKPark JADoh HJChoi YSRho JKim YMKwon YG. Receptor activator of nuclear factor kappaB ligand is a novel inducer of tissue factor in macrophagesCirc Res2010107871-876. 51. Kim J, Min JK, Park JA, Doh HJ, Choi YS, Rho J, Kim YM, Kwon YG: Receptor activator of nuclear factor kappaB ligand is a novel inducer of tissue factor in macrophages. Circ Res 2010;107:871–876.
52.
World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjectsCardiovasc Res1997352-3. 52. World Medical Association Declaration of Helsinki: Recommendations guiding physicians in biomedical research involving human subjects. Cardiovasc Res 1997;35:2–3.
53.
Rosenquist CFledelius CChristgau SPedersen BJBonde MQvist PChristiansen C. Serum CrossLaps One Step ELISA. First application of monoclonal antibodies for measurement in serum of bone-related degradation products from C-terminal telopeptides of type I collagenClin Chem1998442281-2289. 53. Rosenquist C, Fledelius C, Christgau S, Pedersen BJ, Bonde M, Qvist P, Christiansen C: Serum CrossLaps One Step ELISA. First application of monoclonal antibodies for measurement in serum of bone-related degradation products from C-terminal telopeptides of type I collagen. Clin Chem 1998;44:2281–2289.
54.
Veidal SSBay-Jensen ACTougas GKarsdal MAVainer B. Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkersDis Markers20102815-28. 54. Veidal SS, Bay-Jensen AC, Tougas G, Karsdal MA, Vainer B: Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkers. Dis Markers 2010;28:15–28.
55.
Brown MSGoldstein JLKrieger MHo YKAnderson RG. Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteinsJ Cell Biol197982597-613. 55. Brown MS, Goldstein JL, Krieger M, Ho YK, Anderson RG: Reversible accumulation of cholesteryl esters in macrophages incubated with acetylated lipoproteins. J Cell Biol 1979;82:597–613.
56.
Parthasarathy SPrintz DJBoyd DJoy LSteinberg D. Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptorArteriosclerosis19866505-510. 56. Parthasarathy S, Printz DJ, Boyd D, Joy L, Steinberg D: Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor. Arteriosclerosis 1986;6:505–510.
57.
Li ACGlass CK. The macrophage foam cell as a target for therapeutic interventionNat Med200281235-1242. 57. Li AC, Glass CK: The macrophage foam cell as a target for therapeutic intervention. Nat Med 2002;8:1235–1242.
58.
Libby PLee RT. Matrix mattersCirculation20001021874-1876. 58. Libby P, Lee RT: Matrix matters. Circulation 2000;102:1874–1876.
59.
Lemaitre VKim HEForney-Prescott MOkada YD'Armiento J. Transgenic expression of matrix metalloproteinase-9 modulates collagen deposition in a mouse model of atherosclerosisAtherosclerosis2009205107-112. 59. Lemaitre V, Kim HE, Forney-Prescott M, Okada Y, D'Armiento J: Transgenic expression of matrix metalloproteinase-9 modulates collagen deposition in a mouse model of atherosclerosis. Atherosclerosis 2009;205:107–112.
60.
Janssens SLijnen HR. What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models?Cardiovasc Res200669585-594. 60. Janssens S, Lijnen HR: What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models? Cardiovasc Res 2006;69:585–594.
61.
Dorweiler BTorzewski MDahm MOchsenhirt VLehr HALackner KJVahl CF. A novel in vitro model for the study of plaque development in atherosclerosisThromb Haemost200695182-189. 61. Dorweiler B, Torzewski M, Dahm M, Ochsenhirt V, Lehr HA, Lackner KJ, Vahl CF: A novel in vitro model for the study of plaque development in atherosclerosis. Thromb Haemost 2006;95:182–189.
62.
Ruuls SRSedgwick JD. Unlinking tumor necrosis factor biology from the major histocompatibility complex: lessons from human genetics and animal modelsAm J Hum Genet199965294-301. 62. Ruuls SR, Sedgwick JD: Unlinking tumor necrosis factor biology from the major histocompatibility complex: lessons from human genetics and animal models. Am J Hum Genet 1999;65:294–301.
63.
Schoppet MAl-Fakhri NFranke FEKatz NBarth PJMaisch BPreissner KTHofbauer LC. Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Monckeberg's sclerosis and atherosclerosisJ Clin Endocrinol Metab2004894104-4112. 63. Schoppet M, Al-Fakhri N, Franke FE, Katz N, Barth PJ, Maisch B, Preissner KT, Hofbauer LC: Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Monckeberg's sclerosis and atherosclerosis. J Clin Endocrinol Metab 2004;89:4104–4112.
64.
Henriksen KSorensen MGNielsen RHGram JSchaller SDziegiel MHEverts VBollerslev JKarsdal MA. Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidificationJ Bone Miner Res20062158-66. 64. Henriksen K, Sorensen MG, Nielsen RH, Gram J, Schaller S, Dziegiel MH, Everts V, Bollerslev J, Karsdal MA: Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification. J Bone Miner Res 2006;21:58–66.
65.
Fuller KKirstein BChambers TJ. Regulation and enzymatic basis of bone resorption by human osteoclastsClin Sci (Lond)2007112567-575. 65. Fuller K, Kirstein B, Chambers TJ: Regulation and enzymatic basis of bone resorption by human osteoclasts. Clin Sci (Lond) 2007;112:567–575.
66.
Kobayashi KTakahashi NJimi EUdagawa NTakami MKotake SNakagawa NKinosaki MYamaguchi KShima NYasuda HMorinaga THigashio KMartin TJSuda T. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interactionJ Exp Med2000191275-286. 66. Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Morinaga T, Higashio K, Martin TJ, Suda T: Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 2000;191:275–286.
67.
Barascuk NSkjot-Arkil HRegister TCLarsen LByrjalsen IChristiansen CKarsdal MA. Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processesBMC Cardiovasc Disord20101019. 67. Barascuk N, Skjot-Arkil H, Register TC, Larsen L, Byrjalsen I, Christiansen C, Karsdal MA: Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes. BMC Cardiovasc Disord 2010;10:19.

Information & Authors

Information

Published In

cover image ASSAY and Drug Development Technologies
ASSAY and Drug Development Technologies
Volume 10Issue Number 1February 2012
Pages: 69 - 77
PubMed: 22053710

History

Published online: 21 February 2012
Published in print: February 2012
Published ahead of print: 4 November 2011

Permissions

Request permissions for this article.

Topics

Authors

Affiliations

Helene Skjøt-Arkil
Nordic Bioscience A/S, Herlev, Denmark.
Faculty of Health Sciences, Southern University of Denmark, Odense, Denmark.
Natasha Barascuk
Nordic Bioscience A/S, Herlev, Denmark.
Lise Larsen
Nordic Bioscience A/S, Herlev, Denmark.
Morten Dziegiel
Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Kim Henriksen
Nordic Bioscience A/S, Herlev, Denmark.
Morten A. Karsdal
Nordic Bioscience A/S, Herlev, Denmark.

Notes

Address correspondence to:Helene Skjøt-Arkil, MSc PharmNordic BioscienceHerlev Hovedgade 207DK-2730 HerlevDenmark
E-mail: [email protected]

Author Disclosure Statement

M.A.K. owns stock in Nordic Bioscience. All other authors declare no competing financial interests.

Metrics & Citations

Metrics

Citations

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.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF/EPUB

View PDF/ePub

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media

Back to Top