Biologic aspects of vulnerable plaque

Current Opinion in Cardiology

Volumn 17, Issue 6, 2002, Pages 616-625

  Corti, Roberto ^a   Badimon, Juan Jose ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTILIPEMIC AGENT; FAT; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; STATINE DERIVATIVE; THROMBOPLASTIN;

ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; BLOOD CLOTTING; BLOOD VESSEL OCCLUSION; DISEASE COURSE; DRUG TARGETING; HEALING; HUMAN; ISCHEMIA; PRIORITY JOURNAL; REVIEW; RISK FACTOR; RUPTURE; THROMBOSIS;

BIOLOGICAL MARKERS; CORONARY ARTERIOSCLEROSIS; CORONARY CIRCULATION; CORONARY THROMBOSIS; DISEASE PROGRESSION; ENDOTHELIUM, VASCULAR; EVIDENCE-BASED MEDICINE; HUMANS; RISK FACTORS; SYNDROME;

EID: 0036871837     PISSN: 02684705     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001573-200211000-00007     Document Type: Review

References (82)

1. Fuster V, Fayad ZA, Badimon JJ: Acute coronary syndromes: biology. Lancet 1999, 353(suppl 2):S115-9.
2. Libby P: Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001, 104:365-372.
3. Corti R, Fuster V, Badimon JJ, et al.: New understanding of atherosclerosis (clinically and experimentally) with evolving MRI technology in vivo. Ann N Y Acad Sci 2001, 947:181-195; discussion 195-198.
4. Von Rokitansky C: A Manual of Pathological Anatomy. Berlin: Syndheman Soc; 1852:261.
5. Anitschow N, Chalatow S: Uber experimentelle Cholesterinstectase und ihre Bedeutung fur die Entstehung einiger pathologischer Prozesse. Centralbl Allg Path Anot 1913, 1:24.
6. McMillan GC: Historical review of research on atherosclerosis. Adv Exp Med Biol 1995, 369:1-6.
7. Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993, 329:2002-2012.
8. Vanhoutte PM: Endothelium dysfunction and atherosclerosis. Eur Heart J 1997, 18:E19-E29.
9. Luscher TF, Tanner FC, Noll G: Lipids and endothelial function: effects of lipid-lowering and other therapeutic interventions. Curr Opin Lipidol 1996, 7:234-240.
10. Malek AM, Alper SL, Izunmo S: Hemodynamic shear stress and its role in atherosclerosis. JAMA 1999, 282:2035-2042.
11. Ku DN, Giddens DP, Zarins CK, et al.: Pulsatile flow and atherosclerosis in the human carotid bifurcation: positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 1985, 5:293-302.
12. Kinlay S, Libby P, Ganz P: Endothelial function and coronary artery disease. Curr Opin Lipidol 2001, 12:383-389.
13. Lee RT, Yamamoto C, Feng Y, et al.: Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells. J Biol Chem 2001, 276:13847-13851.
14. Mach F, Sauty A, Iarossi AS, et al.: Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. J Clin Invest 1999, 104:1041-1050.
15. Gu L, Okada Y, Clinton SK, et al.: Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 1998, 2:275-281.
16. Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med 1999, 340:115-126.
17. Navab M, Berliner JA, Subbanagounder G, et al.: HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler Thromb Vasc Biol 2001, 21:481-488. • This brief review summarizes the data supporting the evidence that oxidation of LDL is the process responsible for its inflammatory effects within the atherosclerotic lesions. In addition, the authors summarize the potential protective role of HDL to prevent the formation of or to inactivate these inflammatory LDL-derived oxidized phospholipids.
18. Sata M, Saiura A, Kunisato A, et al.: Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002, 8:403-409. •• The authors report for the first time immunohistologic evidence indicating that the smooth muscle cells accumulated within atherosclerotic plaques derive from hematopoietic stem cells and not from smooth muscle cells migrating from the media. As indicated in the article, this intriguing observation could lead to new therapeutic concepts in atherosclerosis.
19. Griendling KK, Alexander RW: Oxidative stress and cardiovascular disease. Circulation 1997, 96:3264-3265.
20. Navab M, Berliner JA, Watson AD, et al.: The yin and yang of oxidation in the development of the fatty streak: a review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 1996, 16:831-842.
21. Lee H, Shi W, Tontonoz P, et al.: Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res 2000, 87:516-521.
22. Llorente-Cortes V, Otero-Vinas M, Hurt-Camejo E, et al.: Human coronary smooth muscle cells internalize versican-modified LDL through LDL receptor-related protein and LDL receptors. Arterioscler Thromb Vasc Biol 2002, 22:387-393.
23. Ross R: Atherosclerosis-an inflammatory disease. N Engl J Med 1999, 340:115-126.
24. Hajjar DP, Haberland ME: Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellular saboteurs. J Biol Chem 1997, 272:22975-22978.
25. Terkeltaub R, Boisvert WA, Curtiss LK: Chemokines and atherosclerosis. Curr Opin Lipidol 1998, 9:397-405.
26. Schecter AD, Rollins BJ, Zhang YJ, et al.: Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997, 272:28568-28573.
27. Luscher TF, Noll G: Is it all in the genes...? Nitric oxide synthase and coronary vasospasm. Circulation 1999, 99:2855-2857.
28. Breslow JL: Genetic differences in endothelial cells may determine atherosclerosis susceptibility. Circulation 2000, 102:5-6.
29. Corti R, Badimon JJ: Value or desirability of hemorheological-hemostatic parameter changes as endpoints in blood lipid-regulating trials. Curr Opin Lipidol 2001, 12:629-637. • This review focus on the effects of LDL cholesterol and of lipid-lowering therapy by statins on vascular biology and blood thrombogenicity.
30. Shah PK, Yano J, Reyes O, et al.: High-dose recombinant apolipoprotein A-l(milano) mobilizes tissue choresterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization. Circulation 2001, 103:3047-3050. • This study demonstrate that one high dose of recombinant Apo A-l(milano) rapidly mobilizes tissue cholesterol and reduces plaque lipid and macrophage content in Apo E-deficient mice, confirming the potential of HDL to rapidly change plaque composition toward a more stable phenotype.
31. Shah PK, Kaul S, Nilsson J, et al.: Exploiting the vascular protective effects of high-density lipoprotein and its apolipoproteins: an idea whose time for testing is coming, part II. Circulation 2001, 104:2498-2502.
32. Shah PK, Kaul S, Nilsson J, et al.: Exploiting the vascular protective effects of high-density lipoprotein and its apolipoproteins: an idea whose time for testing is coming, part I. Circulation 2001, 104:2376-2383. •• This review (parts I and II) extensively summarizes the evidence on the protective vascular effects of HDL at different research levels: basic, experimental, and clinical.
33. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001, 285:2486-2497.
34. Calabresi L, Gomaraschi M, Villa B, et al.: Elevated soluble cellular adhesion molecules in subjects with low HDL choresterol. Arterioscler Thromb Vasc Biol 2002, 22:656-661. • This study provides a possible mechanistic explanation of the increase cardiovascular risk seen in patients with low HDL. Elevated level of adhesion molecules in patients with low HDL may led to plaque initiation and progression as a result of increased accumulation of lipid and inflammatory cells in the subendothelial space.
35. Rubins HB, Robins SJ, Collins D, et al.: Gemfibrozil for the secondary prevention on coronary heart disease in men with low levels of high density lipoprotein cholesterol. N Engl J Med 1999, 341:410-418.
36. Robins SJ, Collins D, Wittes JT, et al.: Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001, 285:1585-1591.
37. Badimon JJ, Badimon L, Fuster V: Regression of atherosclerotic lesions by high density lipoprotein plasma fractions in the cholesterol-fed rabbit. J Clin Invest 1990, 85:1234-1241.
38. Spieker LE, Sudano I, Hurlimann D, et al.: High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 2002, 105:1399-1402. •• This study demonstrates for the first time in vivo in humans that intravenous reconstituted HDL infusion rapidly normalizes endothelium-dependent vasodilation by increasing nitric oxide bioavailability. This is a further explanation (in addition to the reverse cholesterol transport) for the protective effect of HDL from coronary heart disease and illustrates the potential therapeutic benefit of increasing HDL in patients at risk from atherosclerosis.
39. von Eckardstein A, Nofer JR, Assmann G: High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001, 21:13-27. •• The authors review the role of HDL in the reverse cholesterol transport. The authors review the role of HDL in the reverse cholesterol transport. They provide extensive mechanistic explanations on the effects of HDL based on the most recent data with several experimental models (such as genetically modified animals) that help us to understand the lipid metabolism.
40. Hsueh WA, Jackson S, Law RE: Control of vascular cell proliferation and migration by PPAR-gamma: a new approach to the macrovascular complications of diabetes. Diabetes Care 2001, 24:392-397.
41. Marx N, Sukhova G, Murphy C, et al.: Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma (PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol 1998, 153:17-23.
42. Ricote M, Huang J, Fajas L, et al.: Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci U S A 1998, 95:7614-7619.
43. Ricote M, Li AC, Willson TM, et al.: The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998, 391:79-82.
44. Jiang C, Ting AT, Seed B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998, 391:82-86.
45. Pasceri V, Wu HD, Willerson JT, et al.: Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 2000, 101:235-238.
46. Marx N, Bourcier T, Sukhova GK, et al.: PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol 1999, 19:546-551.
47. Kato K, Yamada D, Midorikawa S, et al.: Improvement by the insulin-sensitizing agent, troglitazone, of abnormal fibrinolysis in type 2 diabetes mellitus. Metabolism 2000, 49:662-665.
48. Satoh H, Tsukamoto K, Hashimoto Y, et al.: Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: a new possible role of PPARgamma on vascular endothelial function. Biochem Biophys Res Commun 1999, 254:757-763.
49. Chinetti G, Gbaguidi FG, Griglio S, et al.: CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 2000, 101: 2411-2417. • This study demonstrates, using immunohistologic analysis, increased expression of macrophage cell surface receptors (scavenger receptors CLA-1) in lipid core of human atherosclerotic plaques. They also indicated that the overexpression of the scavenger receptor seems to be mediated by PPARα and PPARγ. These observations identify a potential role for PPARs in cholesterol homeostasis in atherosclerotic lesion macrophages.
50. Fruchart JC: Peroxisome proliferator-activated receptor-alpha activation and high-density lipoprotein metabolism. Am J Cardiol 2001, 88:24N-29N.
51. Fruchart JC, Staels B, Duriez P: PPARS, metabolic disease and atherosclerosis. Pharmacol Res 2001, 44:345-352. • These reviews (references 50, 51) summarize the considerable progress achieved in understanding the molecular basis of lipoprotein metabolism, with particular emphasis in the role of peroxisome proliferator-activated receptor-alpha, the specific transcription factor that, when activated, influences the expression of genes encoding for proteins involved in HDL metabolism.
52. Plutzky J: Peroxisome proliferator-activated receptors in vascular biology and atherosclerosis: emerging insights for evolving paradigms. Curr Atheroscler Rep 2000, 2:327-335. • This review summarizes the recent work implicating PPARα and PPARγ in vascular biology and atherosclerosis. Potential clinical implications are indicated as substances with PPAR mimetic effects are already in use as pharmacologic agents (eg, thiazolidinediones as insulin sensitizers [gamma] and fibric acids as lipid-lowering agents [alpha]).
53. Marx N, Libby P, Plutzky J: Peroxisome proliferator-activated receptors (PPARs) and their role in the vessel wall: possible mediators of cardiovascular risk? J Cardiovasc Risk 2001, 8:203-210. • This review summarizes the cellular-biological effects of PPAR activation in atherosclerotic lesions.
54. Callister TQ, Raggi P, Cooil B, et al.: Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med 1998;339:1972-1978.
55. Corti R, Fayad ZA, Fuster V, et al.: Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive MRI. Circulation 2001, 104:249-252. • This study demonstrates a significant regression of aortic and carotid lipid-rich, nonstenotic plaques in asymptomatic hypercholesterolemic patients after 12 months of treatment with simvastatin. Serial noninvasive magnetic resonance imaging was used to measure the effects of lipid-lowering therapy by simvastatin on the vessel wall. There was a decrease in the vessel wall area of carotid and aortic plaques but no change in the lumen area at 12 months.
56. Zhao XQ, Yuan C, Hatsukami TS, et al.: Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: A case-control study. Arterioscler Thromb Vasc Biol 2001, 21:1623-1629.
57. Crisby M, Nordin-Fredriksson G, Shah PK, et al.: Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001, 103:926-933.
58. Corti R, Fayad ZA, Fuster V, et al.: Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: 2 years follow-up by high-resolution MRI [abstract]. Circulation 2001, 104(suppl II):11-375.
59. Falk E, Shah PK, Fuster V: Coronary plaque disruption. Circulation 1995, 92:657-671.
60. 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, 20:1262-1275. •• This review provides a comprehensive histologic classification of the coronary artery lesions that lead to sudden cardiac death. In addition, to confirm that the majority of the lesions responsible for sudden death (about 60%) are characterized by plaque rupture with superimposed thrombosis, it provides evidence that superficial erosion may account for more than 30% of the cases, whereas calcified nodules appear to be the cause of acute coronary occlusion only rarely.
61. Fernandez-Ortiz A, Badimon JJ, Falk E, et al.: Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 1994, 23:1562-1569.
62. Toschi V, Gallo R, Lettino M, et al.: Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997, 95:594-599.
63. Nemerson Y: Tissue factor and hemostasis. Blood 1988, 71:1-8.
64. Rosenberg RD, Aird WC: Vascular-bed-specific hemostasis and hypercoagulable states. N Engl J Med 1999, 340:1555-1564.
65. Rauch U, Nemerson Y: Tissue factor, the blood, and the arterial wall. Trends Cardiovasc Med 2000, 10:139-143.
66. Giesen PL, Rauch U, Bohrmann B, et al.: Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A 1999, 96:2311-2315.
67. Corti R, Fuster V, Badimon JJ: Strategy for ensuring a better future for the vessel wall. Eur Heart J 2002, 4(suppl 4):A31-A41.
68. Mallat Z, Tedgui A: Current perspective on the role of apoptosis in atherothrombotic disease. Circ Res 2001, 88:998-1003. •• Detailed review of the cell apoptotic phenomena on atherosclerotic disease. The authors report the evidence for apoptosis as a major determinant of the thrombogenicity of the plaque lipid core and a potential contributor to plaque erosion and associated thrombosis and additionally analyze the role of apoptosis on blood thrombogenicity. The authors were the first to associate apoptotic phenomena within atherosclerotic plaque with the release of microparticles into the bloodstream.
69. Geng YJ: Biologic effect and molecular regulation of vascular apoptosis in atherosclerosis. Curr Atheroscler Rep 2001, 3:234-242.
70. Hutter R, Sauter B, Fallon JT, et al.: Macrophages and vascular stellate cells in human carotid plaques are prone to apoptosis and tissue factor expression. J Am Coll Cardiol 2001;37(suppl A):288A.
71. Galis ZS, Khatri JJ: Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 2002, 90:251-262. •• Comprehensive and meticulous review on the effects and regulatory mechanisms of metalloproteinases at the level of atherosclerotic lesions.
72. Moreno PR, Purushothaman RK, Fuster V: Internal elastic lamina in the process of plaque disruption. J Am Coll Cardiol 2001, 37(suppl A):288A-289A.
73. Libby P: Changing concepts of atherogenesis. J Intern Med 2000, 247:349-358.
74. Cowan KN, Jones PL, Rabinovitch M: Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease. J Clin Invest 2000, 105:21-34.
75. Burke AP, Kolodgie FD, Farb A, et al.: Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 2001, 103:934-940. •• Detailed pathologic study providing evidence that silent plaque rupture is a form of wound healing that results in plaque growth and increased percent stenosis. The authors demonstrate that healed plaque ruptures occur in arteries with less cross-sectional area luminal narrowing than acute ruptures and are a frequent finding in men who die suddenly with severe coronary atherosclerosis.
76. Falk E: 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 1985, 71:699-708.
77. Farb A, Burke AP, Tang AL, et al.: Coronary plaque erosion without rupture into a lipid core: a frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996, 93:1354-1363.
78. Rauch U, Crandall J, Osende JI, et al.: Increased thrombus formation relates to ambient blood glucose and leukocyte count in diabetes mellitus type 2. Am J Cardiol 2000, 86:246-249.
79. Osende JI, Badimon JJ, Fuster V, et al.: Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control. J Am Coll Cardiol 2001, 38:1307-1312. • This study demonstrates the relationship between hyperglycemia and increased blood thrombogenicity. Improved glycemic control by aggressive antidiabetic therapy reduced blood thrombogenicity in type 2 diabetes. A significant positive correlation was observed between the reduction in thrombus formation over a thrombogenic substrate (in the extracorporal circulation chamber) and the reduction in HbA1c.
80. Rauch U, Osende JI, Fuster V, et al.: Thrombus formation on atherosclerotic plaques: pathogenesis and clinical consequences. Ann Intern Med 2001, 134:224-238.
81. Rauch U, Osende JI, Chesebro JH, et al.: Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins. Atherosclerosis 2000, 153:181-189. • The relationship between plasma lipid levels and blood thrombogenicity is studied. This study shows similar reduction of blood thrombogenicity in hypercholesterolemic patients treated with simvastatin and pravastatin. The authors report a significant relationship between amounts of thrombus and total cholesterol-to-HDL cholesterol ratio, and a significant increase in the NO-dependent vasodilatation after statin treatment.
82. Sambola A, Hathcock J, Osende J, et al.: Increased circulating tissue factor and blood thrombogenicity in type-2 diabetes. J Am Coll Cardiol 2002, 39(suppl A):202A.