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Arteriosklerose der Koronararterien und Plaque-Progression

Histomorphologische und molekularbiologische Aspekte

Coronary atherosclerosis and progression to unstable plaques

Histomorphological and molecular aspects

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Zusammenfassung

Arteriosklerose führt durch langsame Entwicklung von Stenosen oder durch plötzliche Okklusion des Gefäßlumens durch einen Thrombus zu klinischer Symptomatik. Diese entsteht durch verminderte Perfusion im Myokard (koronare Herzerkrankung, KHK), im zentralen Nervensystem (Apoplexie) oder in den Extremitäten (periphere arterielle Verschlusskrankheit, pAVK). Die KHK stellt die häufigste Manifestation arteriosklerotischer Gefäßläsionen dar und umfasst sowohl die stabile Angina pectoris wie auch die akuten Koronarsyndrome. Arteriosklerose ist eine im Wesentlichen durch Lipoproteinakkumulation in der Arterienwand ausgelöste Erkrankung, welche mit der Formation von Plaques an bestimmten Stellen des arteriellen Systems einhergeht. Die entscheidenden Pathomechanismen umfassen Entzündung, Nekrose, Fibrose und Kalzifizierung. Nach jahrzehntelangem indolenten Verlauf kann es plötzlich zu lebensbedrohlichen akuten Koronarsyndromen kommen. In den allermeisten Fällen ist die zugrunde liegende Läsion eine rupturierte Plaque, deren nekrotisches Material ihres „Kerns“ eine hohe Thrombogenität aufweist. Die arteriosklerotischen Läsionen, die zu einer plötzlichen Thrombosierung mit kompletter oder inkompletter Okklusion führen können, sind das sog. „thin-cap fibroatheroma“, die Plaque-Erosion und das sog. kalzifizierte Knötchen bei stark verkalkten Arterien älterer Individuen, wobei der jeweilige Pathomechanismus bis dato nicht vollständig geklärt ist. Die vorliegende Übersichtsarbeit soll einen Überblick über die Entstehung der wichtigsten arteriosklerotischen Veränderungen und deren Progression zur Plaque-Ruptur bzw. Thrombusformation geben.

Abstract

Atherosclerosis causes clinical symptoms through luminal narrowing by stenosis or by precipitating thrombi that obstruct blood flow to the myocardium (coronary artery disease), central nervous system (ischemic stroke) or lower extremities (peripheral vascular disease). The most common of these manifestations of atherosclerosis is coronary artery disease, clinically presenting as either stable angina or acute coronary syndromes. Atherosclerosis is a mainly lipoprotein-driven disease, which is associated with the formation of atherosclerotic plaques at specific sites of the vascular system through inflammation, necrosis, fibrosis and calcification. In most cases, plaque rupture of a so-called thin-cap fibroatheroma leads to contact of the necrotic core material of the underlying atherosclerotic plaque with blood, resulting in the formation of a thrombus with acute occlusion of the affected (coronary) artery. The atherosclerotic lesions that can cause acute coronary syndromes by formation of a thrombotic occlusion encompass (1) thin-cap fibroatheroma, (2) plaque erosion and (3) so-called calcified nodules in calcified and tortuous arteries of aged individuals. The underlying pathomechanisms remain incompletely understood so far. In this review, the mechanisms of atherosclerotic plaque initiation and progression are discussed.

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Literatur

  1. Lloyd-Jones D, Adams RJ, Brown TM et al (2009) Heart disaese and strike statistics: 2010 update: a report from the American Heart Association. Circulation 121(7):e46–e215

    PubMed  Google Scholar 

  2. Finn AV, Nakano M, Narula J, Kolodgie FD et al (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30:1282–1292

    Article  CAS  PubMed  Google Scholar 

  3. Gronholdt ML, Dalager-Pertersen S, Falk E (1998) Coronary atherosclerosis: determinants of plaque rupture. Eur Heart J 19(Suppl C):C24–C29

    PubMed  Google Scholar 

  4. Farb A, Burke AP, Tang AL et al (1996) Coronary plaque erosion without rupture into a lipid core: a frequent cause of coronary thrombosis in sudden coronary death. Circulation 93:1354–1363

    Article  CAS  PubMed  Google Scholar 

  5. Virmani R, Kolodgie FD, Burke AP et al (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20:1262–1275

    Article  CAS  PubMed  Google Scholar 

  6. Arbustini E, Dal Bello B, Morbini P et al (1999) Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart 82:269–272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Burke AP, Farb A, Malcolm G et al (2001) Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis. Am Heart J 141:S58–S62

    Article  CAS  PubMed  Google Scholar 

  8. Wentzel JJ, Chatzizisis YS, Gijsen FJ et al (2012) Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions. Cardiovasc Res 96:234–243

    Article  CAS  PubMed  Google Scholar 

  9. Bentzon JF, Fumiyuki O, Virmani R et al (2014) Mechanisms of plaque formation and rupture. Circ Res 114:1852–1866

    Article  CAS  PubMed  Google Scholar 

  10. Cheng C, Tempel D, van Haperen R et al (2006) Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 113:2744–2753

    Article  PubMed  Google Scholar 

  11. Glagov S, Weisenberg E, Zarins CK et al (1987) Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371–1375

    Article  CAS  PubMed  Google Scholar 

  12. Nishioka T, Luo H, Eigler NL et al (1996) Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study. J Am Coll Cardiol 25:1571–1576

    Article  Google Scholar 

  13. Varnava AM, Mills PG, Davies MJ (2002) Relationship between coronary artery remodeling and plaque vulnerability. Circulation 105:1571–1576

    Article  Google Scholar 

  14. Burke AP, Kolodgie FD, Farb A et al (2002) Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 105:297–303

    Article  PubMed  Google Scholar 

  15. Ikari Y, McManus BM, Kenyon J et al (1999) Neonatal intima formation in the human coronary artery. Arterioscler Thromb Vasc Biol 93:2036–2040

    Article  Google Scholar 

  16. Orekhov AN, Andreeva ER, Mikhailova IA et al (1998) Cell proliferation in normal and atherosclerotic human aorta: proliferative splash in lipid-rich lesions. Atherosclerosis 139:41–48

    Article  CAS  PubMed  Google Scholar 

  17. Imanishi T, McBride J, Ho Q et al (2000) Expression of cellular FLICE-inhibitory protein in human coronary arteries and in a rat vascular injury model. Am J Pathol 156:125–137

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Fan J, Watanabe T (2003) Inflammatory reactions in the pathogenesis of atherosclerosis. J Atheroscler Thromb 10:63–71

    Article  CAS  PubMed  Google Scholar 

  19. Aikawa M, Rabkin E, Okada Y et al (1998) Lipid lowering by diet reduces matrixmetalloprotease activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation 97:2433–2444

    Article  CAS  PubMed  Google Scholar 

  20. Hoff HF, Bradley WA, Heidemann CL et al (1979) Characterization of low-density lipoprotein-like particle in the human aorta from grossly normal and atherosclerotic regions. Biochim Biophys Acta 573:361–374

    Article  CAS  PubMed  Google Scholar 

  21. Smith EB, Slater RS (1972) The microdissection of large atherosclerotic plaques to give morphologically and topographically defined fractions for analysis: 1. The lipids in the isolated fractions. Atherosclerosis 15:37–56

    Article  CAS  PubMed  Google Scholar 

  22. Sakakura K, Nakano M, Otsuka F et al (2013) Pathophysiology of atherosclerosis plaque progression. Heart Lung Circ 22:399–411

    Article  PubMed  Google Scholar 

  23. Kockx MM, De Meyer GR, Muhring J et al (1998) Apoptosis and related proteins in different stages of atherosclerotic plaques. Circulation 97:2307–2315

    Article  CAS  PubMed  Google Scholar 

  24. Kolodgie FD, Burke AP, Nakazawa G et al (2007) Is pathologic intimal thickening the key to understanding early plaque progression in human atherosclerotic disease? Arterioscler Thromb Vasc Biol 27:986–989

    Article  CAS  PubMed  Google Scholar 

  25. Bao L, Li Y, Deng SX et al (2006) Sitosterol-containing lipoproteins trigger free sterol-induced caspase-independent death in ACAT-competent macrophages. J Biol Chem 281:33635–33649

    Article  CAS  PubMed  Google Scholar 

  26. Tabas I (2000) Cholesterol and phospholipid metabolism in macrophages. Biochim Biophys Acta 1529:164–174

    Article  CAS  PubMed  Google Scholar 

  27. Tabas I, Marathe S, Keesler GA et al (1996) Evidence that the initial up-regulation of phosphatidylcholine biosynthesis in free cholesterol-loaded macrophages is an adaptive response that prevents cholesterol-induced cellular necrosis in advanced atherosclerosis. J Biol Chem 271:22773–22781

    Article  CAS  PubMed  Google Scholar 

  28. Kolodgie FD, Virmani R, Burke AP et al (2004) Pathologic assessment of the vulnerable human coronary plaque. Heart 90:1385–1391

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Burke AP, Farb A, Malcom GT et al (1997) Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 336:1276–1282

    Article  CAS  PubMed  Google Scholar 

  30. Burke AP, Farb A, Malcom GT et al (1999) Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 281:921–926

    Article  CAS  PubMed  Google Scholar 

  31. Sukhova GK, Schönbeck U, Rabkin E et al (1999) Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation 99:2503–2509

    Article  CAS  PubMed  Google Scholar 

  32. Gijsen FJ, Wentzel JJ, Thury A et al (2008) Strain distribution over plaques in human coronary arteries relates to shear stress. Am J Physiol Heart Circ Physiol 295:H1608–H1614

    Article  CAS  PubMed  Google Scholar 

  33. Vengrenyuk Y, Carlier S, Xanthos S et al (2006) A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci 103:14678–14683

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Kolodgie FD, Narula J, Burke AP et al (2000) Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am J Pathol 157:1259–1268

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874

    Article  CAS  PubMed  Google Scholar 

  36. Steinberg D (2002) Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat Med 8:1211–1217

    Article  CAS  PubMed  Google Scholar 

  37. Witztum JL, Steinberg D (2001) The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Trends Cardiovasc Med 11:93–102

    Article  CAS  PubMed  Google Scholar 

  38. Li AC, Glass CK (2002) The macrophage foam cell as a target for therapeutic intervention. Nat Med 8:1235–1242

    Article  CAS  PubMed  Google Scholar 

  39. Krieger M (1997) The other side of scavenger receptors: pattern recognition for host defence. Curr Opin Lipidol 8:275–280

    Article  CAS  PubMed  Google Scholar 

  40. Ionita MG, Arslan F, de Kleijn DP et al (2010) Endogenous inflammatory molecules engage Toll-like receptors in cardiovascular disease. J Innate Immun 2:307–315

    Article  CAS  PubMed  Google Scholar 

  41. Muzio M, Mantovani A (2001) Toll-like receptors (TLRs) signalling and expression pattern. J Endotoxin Res 7:297–300

    Article  CAS  PubMed  Google Scholar 

  42. Faure E, Thomas L, Xu H et al (2001) Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation. J Immunol 166:2018–2024

    Article  CAS  PubMed  Google Scholar 

  43. Newby AC (2008) Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol 28:2108–2114

    Article  CAS  PubMed  Google Scholar 

  44. Kumamoto M, Nakashima Y, Sueishi K (1995) Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol 26:450–456

    Article  CAS  PubMed  Google Scholar 

  45. Sluimer JC, Kolodgie FG, Bijnens AP et al (2009) Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions: relevance of compromised structural integrity for intraplaque microvascular leakage. J Am Coll Cardiol 53:1517–1527

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Davies MJ, Thomas A (1984) Thrombosis and acute coronary artery lesions in sudden cardiac ischemic death. N Engl J Med 310:1137–1140

    Article  CAS  PubMed  Google Scholar 

  47. Koloodgie FD, Gold HK, Burke AP et al (2003) Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 349:2316–2325

    Article  Google Scholar 

  48. Davies MJ (2000) The pathophysiology of acute coronary syndromes. Heart 83:361–366

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Kolodgie FD, Burke AP, Farb A et al (2001) The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol 16:285–292

    Article  CAS  PubMed  Google Scholar 

  50. van der Wal AC, Becker AE, van der Loos CM et al (1994) Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89:36–44

    Article  PubMed  Google Scholar 

  51. Falk E (1983) Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Br Heart J 50:127–134

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Gough PJ, Gomez IG, Wille PT et al (2006) Macrophage expression of MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest 116:59–69

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Mittleman MA, Mostofsky E (2011) Physical, psychological and chemical triggers of acute cardiovascular events: preventive strategies. Circulation 124:346–354

    Article  PubMed Central  PubMed  Google Scholar 

  54. Muller JE, Stone PH, Turi ZG et al (1985) Circadian variation in the frequency of onset of myocardial infarction. N Engl J Med 313:1315–1322

    Article  CAS  PubMed  Google Scholar 

  55. Martin JF, Kristensen SD, Mathur A et al (2012) The causal role of megacaryocyte-platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol 9:658–670

    Article  CAS  PubMed  Google Scholar 

  56. Kramer MC, Rittersma SZ, de Winter RJ et al (2010) Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. Am J Coll Cardiol 55:122–132

    Article  Google Scholar 

  57. Fernandez-Ortiz A, Badimon JJ, Falk E et al (1994) Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 23:1562–1569

    Article  CAS  PubMed  Google Scholar 

  58. Virmani R, Burke AP, Farb A et al (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47:C13–C18

    Article  CAS  PubMed  Google Scholar 

  59. Hao H, Gabbiani G, Camenzind E et al (2006) Phenotypic modulation of intima and media smooth muscle cells in fatal cases of coronary artery lesions. Arterioscler Thromb Vasc Biol 26:326–332

    Article  CAS  PubMed  Google Scholar 

  60. Rautou PE, Vion AC, Amabile N et al (2011) Microparticles, vascular function, and atherothrombosis. Circ Res 109:593–606

    Article  CAS  PubMed  Google Scholar 

  61. Falk E (1985) Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 71:699–708

    Article  CAS  PubMed  Google Scholar 

  62. Sachdeva A, Cannon CP, Deedwania PC et al (2009) Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136.905 hospitalizations in GET with the guidelines. Am Heart J 157:111e2–117e2

    Article  Google Scholar 

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinik Essen, Essen, Deutschland

    Jeremias Wohlschlaeger, S. Bertram, D. Theegarten, T. Hager & H.A. Baba

  2. Institut für Pathologie, Evang.-luth. Diakonissenanstalt zu Flensburg, Flensburg, Deutschland

    Jeremias Wohlschlaeger

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  1. Jeremias Wohlschlaeger
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  2. S. Bertram
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  3. D. Theegarten
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Correspondence to Jeremias Wohlschlaeger.

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Wohlschlaeger, J., Bertram, S., Theegarten, D. et al. Arteriosklerose der Koronararterien und Plaque-Progression. Herz 40, 837–844 (2015). https://doi.org/10.1007/s00059-015-4341-0

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