Résumés
Résumé
L’athérosclérose est une maladie inflammatoire de la paroi artérielle. Ses manifestations ischémiques sont essentiellement dues à la formation d’un thrombus luminal au contact de la plaque lorsque l’endothélium est dénudé ou lorsque la plaque se rompt, exposant ainsi au sang circulant du matériel thrombogène. L’inflammation et l’apoptose interviennent dans l’instabilité de la plaque, en favorisant sa rupture et la thrombose qui s’ensuit. L’inflammation conduit à la mort des cellules musculaires lisses et à la dégradation du collagène, rendant ainsi fragile le tissu de soutien de la plaque. L’apoptose joue quant à elle un rôle essentiel dans la thrombogénicité du noyau lipidique de la plaque. Stabiliser les plaques pour empêcher l’ischémie est l’objectif qui anime toutes les recherches dans ce domaine.
Summary
Atherosclerosis is an inflammatory disease of the arterial wall. Ischemic manifestations of atherosclerosis are mainly due to thrombus formation upon a superficially eroded (denudation of luminal ndothelium, 40% of cases) or deeply ruptured (fibrous cap rupture, 60% of cases) plaques. Recent studies have unraveled potentially critical roles for both inflammatory and apoptotic processes in plaque destabilization leading to thrombus formation. Pro-inflammatory mediators have been particularly implicated in the loss of smooth muscle cell and the promotion of collagen degradation that are responsible for fibrous cap rupture, whereas apoptosis has been identified as one of the major determinants of plaque thrombogenicity.
Parties annexes
Références
- 1. Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-74.
- 2. Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262-75.
- 3. Burke AP, Kolodgie FD, Farb A, et al. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 2002; 105: 297-303.
- 4. Burke AP, Farb A, Malcom GT, et al. Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 1999; 281: 921-6.
- 5. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105: 1135-43
- 6. Meuwissen M, Piek JJ, van der Wal AC, et al. Recurrent unstable angina after directional coronary atherectomy is related to the extent of initial coronary plaque inflammation. J Am Coll Cardiol. 2001; 37: 1271-6.
- 7. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 2002; 90: 251-62.
- 8. Gupta S, Pablo AM, Jiang X, et al. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest 1997; 99: 2752-61.
- 9. Whitman SC, Ravisankar P, Daugherty A. Interleukin-18 enhances atherosclerosis in apolipoprotein E-/- mice through release of interferon-gamma. Circ Res 2002; 90: E34-8.
- 10. Mallat Z, Corbaz A, Scoazec A, et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 2001; 104: 1598-603.
- 11. Lee TS, Yen HC, Pan CC, Chau LY. The role of interleukin 12 in the development of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 1999; 19: 734-42.
- 12. Schonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res 2001; 89: 1092-103.
- 13. Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall. Circ Res 2001; 88: 877-87.
- 14. Mallat Z, Besnard S, Duriez M, et al. Protective role of interleukin-10 in atherosclerosis. Circ Res 1999; 85: E17-24.
- 15. Smith DA, Irving SD, Sheldon J, et al. Serum levels of the antiinflammatory cytokine interleukin-10 are decreased in patients with unstable angina. Circulation 2001; 104: 746-9.
- 16. Mallat Z, Gojova A, Marchiol-Fournigault C, et al. Inhibition of transforming growth factor-β signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res 2001; 89: 930-4.
- 17. Mallat Z, Corbaz A, Scoazec A, et al. Interleukin-18/interleukin-18 binding protein signalling modulates atherosclerotic lesion development and stability. Circ Res 2001; 89: E41-5.
- 18. Tedgui A, Mallat Z. Apoptosis as a determinant of atherothrombosis. Thromb Haemost 2001; 86: 420-6.
- 19. Chang MK, Bergmark C, Laurila A, et al. Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: evidence that oxidation-specific epitopes mediate macrophage recognition. Proc Natl Acad Sci USA 1999; 96: 6353-8.
- 20. Toschi V, Gallo G, Lettino M, et al. Tissue factor modulates thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95: 594-9.
- 21. Flynn PD, Byrne CD, Baglin TP, et al. Thrombin generation by apoptotic vascular smooth muscle cells. Blood 1997; 89: 4378-84.
- 22. Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant. Blood 1997; 89: 2429-42.
- 23. Aupeix K, Hugel B, Martin T, et al. The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J Clin Invest 1997; 99: 1546-54.
- 24. Mallat Z, Hugel B, Ohan J, et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-53.
- 25. Kolodgie FD, Narula J, Burke AP, et al. Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am J Pathol 2000; 157: 1259-68.
- 26. van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994; 89: 436-40.
- 27. Kolodgie FD, Burke AP, Farb A, et al. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion. Arterioscler Thromb Vasc Biol 2002; 22: 1642-8.
- 28. Tricot O, Mallat Z, Heymes C, et al. Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation 2000; 101: 2450-3.
- 29. Mallat Z, Tedgui A. Current perspective on the role of apoptosis in atherothrombotic disease. Circ Res 2001; 88: 998-1003.
- 30. Giesen PL, Rauch U, Bohrmann B, et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-5.
- 31. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies (part I). Circulation 2003; 108: 1664-72.