Plaques rupture

Plaque rupture and the ensuing thrombosis commonly cause the most dreaded acute complications of... 

Endothelial dysfunction, inflammation, and the formation of fatty streaks contribute to the formation of atherosclerotic coronary artery plaques, the underlying cause of coronary artery disease (CAD). The predominant cause of ACS, in more than 90% of patients, is atheromatous plaque rupture, Assuring, or erosion of an unstable atherosclerotic plaque that occludes less than 50% of the coronary lumen prior to the event, rather than a more stable 70% to 90% stenosis of the coronary artery.3 Stable stenoses are characteristic of stable angina. 

Acute coronary syndromes Ischemic chest discomfort at rest, most often accompanied by ST-segment elevation, ST-segment depression, or T-wave inversion on the 12-lead electrocardiogram. Furthermore, it is caused by plaque rupture and partial or complete occlusion of the coronary artery by thrombus. Acute coronary syndromes include myocardial infarction and unstable angina. Former terms used to describe types of acute coronary syndromes include Q-wave myocardial infarction, non-Q-wave myocardial infarction, and unstable angina. 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

Repeated injury and repair within an atherosclerotic plaque eventually lead to a fibrous cap protecting the underlying core of lipids, collagen, calcium, and inflammatory cells such as T lymphocytes. Maintenance of the fibrous plaque is critical to prevent plaque rupture and subsequent coronary thrombosis. 

A number of factors increase the risk of disruption of the plaque the presence of a considerable amount of fat in the plaque the effects of physical stress on the vessel wall, particularly in the hypertensive patient and the activity of macrophages. Macrophages release proteases (e.g. colla-genase, elastase) which lead to breakdown of the plaque. Rupture of the plaque produces fissures that are sites for aggregation of platelets. Fragments from the rupture can occlude blood vessels. 

A.C. Newby, Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol. Rev. 85 (2005) 1-31. 

Boyle JJ. Macrophage activation in atherosclerosis pathogenesis and pharmacology of plaque rupture. 

Shah PK. Pathophysiology of plaque rupture and the concept of plaque stabilization. Cardiol Clin. 2003 21 303-314. 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

The pathogenic mechanism of ACS is that coronary arteriosclerotic plaques rupture and erode leading to thrombosis. Once injury to the coronary endothelial cells occurs, collagen and von Willebrand factor exposed to subendothelial matrix adhere to platelets. Consequently, these platelets are... 

Critical role of thrombin in thrombogenesis. Thrombin plays a critical and central role in thrombogenesis through platelet activation, fibrin generation, and clot stabilization at the site of arterial disruption, which are caused by percutaneous coronary intervention or plaque rupture in acute coronary syndromes. 

Acute coronary syndromes (ACS) are a major cause of morbidity and mortality. They are characterized by intracoronary thrombus formation at the site of atherosclerotic plaques. Coronary thrombosis is the underlying mechanism in the transition from stable angina to the unstable angina (UA) syndrome, characterized by embolization of the developed thrombus and atherosclerotic plaque rupture. 

Schroeder AR Falk E. Pathophysiology and inflammatory aspects of plaque rupture. Cardiol Clin 1996 14 21 1-220,... 

Fuster V Stein B, Ambrose JA, Badimon L, Badimon JJ, ChesebroJH. Atherosclerotic plaque rupture and thrombosis, Evolving concepts. Circulation 1990 82(suppl 3) 1147—1159. 

Klein LW, Clinical implications and mechanisms of plaque rupture in the acute coronary syndromes, Am Heart Hosp J 2005 3(4) 249-255,... 

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 ... 

---