The accumulation of specific types of proteoglycans in eroded plaques: a role in coronary thrombosis in the absence of rupture.

Abstract

Although fibrous cap rupture is the primary cause of coronary thrombosis, plaque erosion is responsible for 30%-40% of acute thrombotic events. The interface of the eroded surface involves a denuded endothelium allowing direct contact of the platelet/fibrin thrombus with the underlying lesion. This review discusses the putative role of extracellular matrix molecules, in particular proteoglycans/hyaluronan, in the development of acute coronary thrombosis associated with erosion. The plaque/thrombus interface in erosion presents a unique surface since it consists of predominantly SMCs and proteoglycans with minimal or no inflammation. The lack of significant inflammation raises the possibility that erosion represents chronic wounding rather than true atherogenesis. The abundance of proteoglycan and hyaluronan matrix suggests their potential role in the development of thrombosis. Matrix changes may contribute to endothelial loss, the magnitude of the thrombotic event, or both. Versican facilitates platelet adhesion at low shear and cooperates with collagen to promote platelet aggregation. Further, versican may, in part, regulate water content and in turn support coagulation because water-dependent functionality of anticoagulation molecules. Finally, experimental models of plaque erosion are currently being developed guided by the premise that the loss of surface endothelium together with other procoagulant factors may underlie the development of platelet-rich thrombi. The loss of endothelium and exposure of a potentially procoagulant versican-hyaluronan matrix may be largely responsible for plaque erosion. The development of relevant animal models should allow further insight into the pathophysiology of coronary thrombosis in the absence of rupture.