Pathophysiology of Atherosclerotic Plaque Development and Rupture: An Overview

Luis E. P. Rohde; Richard T. Lee

doi:10.1055/s-2004-815692

Seminars in Vascular Medicine, Table of Contents

Semin Vasc Med 2003; 03(4): 347-354
DOI: 10.1055/s-2004-815692

ETIOLOGY OF ACS

Pathophysiology of Atherosclerotic Plaque Development and Rupture: An Overview

Luis E.P. Rohde¹ , Richard T. Lee²

¹Hospital de Clínicas de Porto Alegre, Medical Post-Graduation Program, Medical School of Rio Grande do Sul Federal University, Porto Alegre, Brazil
²Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Abstract

ABSTRACT

Atherosclerosis is predominantly a clinically silent process, and a substantial percentage of patients are first aware of its consequences through the acute and catastrophic event of thrombosis. Extensive basic and clinical research in the 1990s revealed that plaque disruption initiates the majority of thromboses. Furthermore, recent studies indicate that inflammation plays a major role in the pathophysiology, from initiation of the atheroma to the actual thrombosis itself. Attention has now focused on morphological, mechanical, and biochemical characteristics that increase plaque vulnerability, as determination of these features may allow identification of plaques that are most likely to cause symptoms and acute events in the future. This article reviews basic pathophysiologic aspects of atherosclerotic plaque development and rupture to provide the necessary background for understanding the crucial role of inflammation in acute coronary syndromes.

KEYWORDS

Atherosclerosis - inflammation - plaque rupture - unstable atheroma

Full Text

References

REFERENCES

1 Libby P. Molecular bases of acute coronary syndromes. Circulation . 1995; 91 2844-2850
2 Shah P K. New insights into the pathogenesis and prevention of acute coronary syndromes. Am J Cardiol . 1997; 79 17-23
3 Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med . 1999; 340 115-126
4 Davies M J, Gordon J L, Pigott R, Woolf N, Katz D, Kyriakopoulos A. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Pathol . 1993; 171 223-229
5 O'Brien K D, Allen M D, McDonald T O. et al . Vascular cell endothelial molecule-1 is expressed in human coronary atherosclerotic plaques. J Clin Invest . 1993; 92 945-951
6 Li H, Cybulsky M I, Gimbrone Jr A M, Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb . 1993; 13 197-204
7 Nageh M F, Sandberg E T, Marotti K R. et al . Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol . 1997; 17 1517-1520
8 Johnson R C, Chapman S M, Dong Z M. et al . Absence of P-selectin delays fatty streak formation in mice. J Clin Invest . 1997; 99 1037-1043
9 Peter K, Nawroth P, Conradt C. et al . Circulating vascular adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. Arterioscler Thromb Vasc Biol . 1997; 17 505-512
10 Rohde L E, Lee R T, Rivero J. et al . Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. Arterioscler Thromb Vasc Biol . 1998; 18 1765-1770
11 Libby P, Ridker P M, Maseri A. Inflammation and atherosclerosis. Circulation . 2002; 105 1135-1143
12 Rohde L E, Hennekens C H, Ridker P M. Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. Am J Cardiol . 1999; 84 1018-1022
13 Rohde L E, Hennekens C H, Ridker P M. A cross-sectional study of soluble intercellular adhesion molecule-1 and cardiovascular risk factors in apparently healthy men. Arterioscler Thromb Vasc Biol . 1999; 19 1595-1599
14 Thompson S G, Kienast J, Pyke S DM, Haverkate F, van de Loo C W J, for the European Concerted Action on Thrombosis, and Disabilities Angina Pectoris Study Group. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med . 1995; 332 635-641
15 Harverkate F, Thompson S G, Pyke S D, Gallimore J R, Pepys M G. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action in Thrombolysis and Disabilities Angina Pectoris Study Group. Lancet . 1997; 349 462-466
16 Kuller L H, Tracy R P, Shaten J, Meinhahn E N, for the MRFIT Research Group. Relation of C-reactive protein and coronary artery disease in the MRFIT nested case-control study. Am J Epidemiol . 1996; 144 537-547
17 Tracy R P, Lemaitre R N, Psaty B M. et al . Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol . 1997; 17 1121-1127
18 Ridker P M, Cushman M, Stampfer M J, Tracy R P, Hennekens C H. Inflammation, aspirin, and risks of cardiovascular disease in apparently healthy men. N Engl J Med . 1997; 336 973-979
19 Ridker P M, Buring J E, Shih J, Matias M, Hennekens C H. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation . 1998; 98 731-733
20 Ridker P M, Rifai N, Pfeffer M A, for the Cholesterol and Recurrent Events (CARE) Investigators. et al . Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation . 1998; 98 839-844
21 Ridker P M, Rifai N, Clearfield M. et al . Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med . 2001; 344 1959-1965
22 Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link?. Lancet . 1997; 350 430-436
23 Kol A, Sukhova G K, Lichtman A H. et al . Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage TNF-α and matrix metalloproteinase expression. Circulation . 1998; 98 300-307
24 Danesh J, Whincup P, Walker M. et al . Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis. BMJ . 2000; 321 208-213
25 Lee R T, Schoen F J. Pathology of unstable coronary plaque. In: Rutherford JD, ed. Unstable Angina New York: Marcel Dekker 1991: 1-25
26 Farb A, Burke A P, Tang A L. 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
27 Born G VR, Richardson P D. Mechanical properties of human atherosclerosis. In: Glagov S, Newman W, Schaffer S, eds. Pathobiology of the Human Atherosclerotic Plaques New York: Springer-Verlag 1990: 413-424
28 Davies M J, Thomas A C. Plaque fissuring-the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J . 1985; 53 363-373
29 Richardson P D, Davies M J, Born G VR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet . 1989; 2 941-944
30 Lee R T, Libby P. The unstable atheroma. Arterioscler Thromb Vasc Biol . 1997; 17 1859-1867
31 Libby P, Lee R T. Role of activated macrophages and T-lymphocytes in rupture of coronary plaques. In: Braumwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine Update. Vol. 2. Philadelphia: WB Saunders 1995: 1-9
32 Amento E P, Ehsani N, Palmer H, Libby P. Cytokines positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb . 1991; 11 1223-1230
33 Geng Y-J, Henderson L, Levesque E. et al . Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol . 1997; 17 2200-2208
34 Nikkari S T, O'Brien K D, Ferguson M. et al . Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation . 1995; 92 1393-1398
35 Dellery C M, McEwan J R, Henney A M. Matrix metalloproteinases and cardiovascular disease. Circ Res . 1995; 77 863-868
36 Galis Z S, Muszynski M, Sukhova G K. et al . Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res . 1994; 75 181-189
37 Lee E, Grodzinsky A J, Libby P, Clinton S K, Lark M W, Lee R T. Human vascular smooth muscle cell-monocyte interactions and metalloproteinase secretion in culture. Arterioscler Thromb Vasc Biol . 1995; 15 2283-2289
38 Galis Z S, Sukhova G, Kranzhofer R, Clark S, Libby P. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci USA . 1995; 92 402-406
39 Shah P K, Falk E, Badimon J J. et al . Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications of plaque rupture. Circulation . 1995; 92 1565-1569
40 Lendon C L, Davies M J, Born G VR, Richardson P D. Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis . 1991; 87 87-90
41 Lee R T, Grodzinsky A J, Franf E H, Kamm R D, Schoen F J. Structure dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaque. Circulation . 1991; 83 1764-1770
42 Loree H M, Grodzinsky A J, Park S Y, Gibson L J, Lee R T. Static circumferential modulus of human atherosclerotic tissue. J Biomech . 1994; 27 195-204
43 Loree H M, Tobias B J, Gibson L J, Kamm R D, Small D M, Lee R T. Mechanical properties of model atherosclerotic lesion lipid pools. Arterioscler Thromb . 1994; 14 230-234
44 Rohde L E, Lee R T. Mechanical stress and strain and the vulnerable atherosclerotic lesion. In: Fuster V, ed. The Vulnerable Atherosclerotic Plaque: Understanding, Identification and Modification Armonk, NY: Futura Publishing 1999: 305-316
45 Loree H M, Kamm R D, Stringfellow R G, Lee R T. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res . 1992; 71 850-858
46 Cheng G C, Loree H M, Kamm R D, Fishbein M C, Lee R T. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation. Circulation . 1993; 87 1179-1187
47 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation . 2001; 104 365-372
48 Bogaty P, Hackett D, Davies G, Maseri A. Vasoreactivity of the culprit lesion in unstable angina. Circulation . 1994; 90 5-11
49 Bevilacqua M P, Schleef R, Gimbrone M AJ. et al . Regulation of the fibrinolytic system of cultured human vascular endothelium by interleukin 1. J Clin Invest . 1986; 78 587-591
50 Mach F, Schonbeck U, Bonnefoy J-Y, Pober J S, Libby P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation . 1997; 96 396-399
51 Mach F, Schönbeck U, Sukhova G K, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signaling. Nature . 1998; 394 200-203
52 Marx N, Sukhova G K, Collins T. et al . PPAR-α activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation . 1999; 99 3125-3131
53 Marx N, Mackman N, Schoenbeck U. et al . PPAR-α activators inhibit tissue factor expression and activity in human monocytes. Circulation . 2001; 103 213-219
54 Kato H. Regulation of functions of vascular wall cells by tissue factor pathway inhibitor: basic and clinical aspects. Arterioscler Thromb Vasc Biol . 2002; 22 539-548
55 Yin X, Yutani C, Ikeda Y. et al . Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposomes markedly reduces restenosis in atherosclerotic arteries. Cardiovasc Res . 2002; 56 454-463
56 Goldstein J A, Demetriou D, Grines C L, Pica M, Shoukfen M, O'Neill W W. Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med . 2000; 343 915-922
57 Asakura M, Ueda Y, Yamaguchi O. et al . Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. J Am Coll Cardiol . 2001; 37 1284-1288
58 Rioufol G, Finet G, Ginon I. et al . Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation . 2002; 106 804-808
59 Spagnoli L G, Bonanno E, Mauriello A. et al . Multicentric inflammation in epicardial coronary arteries of patients dying of acute myocardial infarction. J Am Coll Cardiol . 2002; 40 1579-1588
60 Buffon A, Biasucci L M, Liuzzo G, D'onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina. N Engl J Med . 2002; 347 5-12
61 Lee R T, Loree H M, Cheng G C, Lieberman E H, Jaramillo N, Schoen F J. Computational structural analysis based on intravascular ultrasound imaging before in vitro angioplasty: prediction of plaque fracture locations. J Am Coll Cardiol . 1993; 21 777-782
62 Hatsukami T S, Ross R, Polissar N L, Yuan C. Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation . 2000; 102 959-964
63 Yuan C, Mitsumori L M, Ferguson M S. et al . In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques. Circulation . 2001; 104 2051-2056
64 Nair A, Kuban B D, Tuzcu M, Schoenhagen P, Nissen S E, Vince D G. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation . 2002; 106 2200-2206
65 Stefanidis C, Diamantopoulos L, Vlachopoulos C. et al . Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo. A new method of detection by application of a special thermography catheter. Circulation . 1999; 99 1965-1971
66 Stefanidis C, Toutouzaz K, Tsiamis E. et al . Increased local temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention. J Am Coll Cardiol . 2001; 37 1277-1283