Plaque Disruption and Thrombosis

Acute coronary syndromes (unstable angina, acute myocardial infarction, and ischemic sudden death) result from coronary thrombosis superimposed on an atherosclerotic plaque. Thrombosis is generally a consequence of disruption of the atherosclerotic plaque in the form of a fissure/rupture in the fibrous cap overlying a lipid-rich pool or superficial endothelial erosion covering a smooth muscle and proteoglycan-rich matrix with or without a lipid-core. Approximately 2/3 of acute coronary syndromes evolve from atherosclerotic plaques that are minimally or mildly obstructive of the lumen before the acute event. Inflammation with accumulation of activated mononuclear cells may play a potential role in plaque disruption through the elaboration of proteases, such as matrix degrading neutral metalloproteinases and other proteases, inhibition of function and/or survival, or promotion of apoptosis of matrix synthesizing smooth muscle cells. Inflammation may also contribute to thrombosis after plaque disruption by providing a source for tissue factor in the plaque. Inflammation in the plaque may result from accumulation of modified lipids, oxidant and hemodynamic stress, and infectious agents, such as Chlamydia pneumoniae or pro-inflammatory triggers from distant sites of infection and inflammation (eg, chronic gingivitis and chronic bronchitis). Improved insights into the pathophysiology of plaque disruption and thrombosis are likely to provide new and improved methods of stabilizing atherosclerotic disease process.