Atherothrombosis: mechanisms and clinical therapeutic approaches

Abstract

Eroded or disrupted atherosclerotic plaques act as a substrate for thrombosis, leading to ischemic coronary artery and cerebrovascular disease. Plaques vary greatly in composition, size, and the degree of stenosis they cause. Plaques can be categorized based on these features, which helps to estimate the likelihood of rupture and subsequent thrombosis. Vascular plaques often begin at regions with low and oscillatory shear forces that cause chronic minimal endothelial damage or dysfunction. Lipoproteins enter the vessel wall, promoting the recruitment of monocytes, which imbibe lipids and become foam cells. Smooth muscle cells invade these early plaques, producing connective tissue fibrils that form a fibrous cap over the lipid center; rupture of this cap is an important cause of thrombosis. Passive plaque disruption occurs when physical forces cause cap rupture; active disruption occurs when the cap is attacked by macrophages and proteolytic enzymes. Tissue factor is one of many factors within plaque that stimulates thrombosis.