title: Toward the quiescent coronary plaque.
abstract: The treatment of coronary atherosclerosis requires an understanding of the pathophysiology of plaque rupture. The rupture of lipid-laden, macrophage-rich plaques initiates unstable angina, acute myocardial infarction and sudden cardiac death. Plaque rupture occurs when the circumferential tension on a plaque exceeds its tensile strength, an event that cannot be predicted by coronary angiography. The incidence of plaque rupture appears to be reduced in patients receiving cholesterol-lowering therapy, beta-adrenergic blocking agents and, possibly, angiotensin-converting enzyme inhibitors and antioxidants. Not all ruptured coronary plaques produce an acute coronary syndrome. The consequences of plaque rupture depend on the extent of thrombus formation over the fissured plaque. This is determined by flow characteristics within the vessel as well as the activity of the thrombotic and fibrinolytic systems. Recent advances in cardiovascular molecular biology, coronary diagnostic techniques and cardiac therapeutics have opened windows of opportunity to study and modify the factors leading to plaque rupture. The local modification of gene expression to alter plaque composition and to elucidate and subsequently inhibit the prothrombotic and fibrinolytic defects that promote coronary thrombosis may, in future, prevent plaque rupture and its consequences. The application of such a concerted interdisciplinary approach promises a paradigm shift in the management of coronary artery disease toward the prevention of plaque rupture and its sequelae.
authors.affiliation: Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195.
authors.forename: A I
authors.initials: AI
authors.lastname: MacIsaac
authors.forename: J D
authors.initials: JD
authors.lastname: Thomas
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000789:Angina, Unstable / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D003328:Coronary Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D005342:Fibrinolysis; D015870:Gene Expression; D006439:Hemodynamics; D018056:Hemorheology; D006801:Humans; D015994:Incidence; D008955:Models, Cardiovascular; D008967:Molecular Biology; D009203:Myocardial Infarction / Q000209:etiology* / Q000503:physiopathology; D012307:Risk Factors; D013314:Stress, Mechanical; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000924:Anticholesteremic Agents; D000975:Antioxidants