Targeting the prevention of plaque rupture as a new strategy for prevention of acute arterial cardiovascular events

Acute arterial cardiovascular disease is usually caused by the sudden thrombotic occlusion of a vessel that is critical for maintaining adequate tissue perfusion and that contains an atherosclerotic plaque. Due to a myriad of processes within this plaque, rupture of its fibrous cap may occur, thereby exposing highly procoagulant material to the circulating blood, leading to occlusive thrombus formation and subsequent ischemia or infarction. In particular, inflammatory cells bearing tissue factor at their surface play a pivotal role in this mechanism, as tissue factor has been found to be the principal activator of the coagulation cascade, leading to the generation of thrombin and subsequent conversion of fibrinogen to fibrin. Hence, pharmacological strategies aimed at the prevention and treatment of acute cardiovascular disease thus far mainly focus on the reduction of atherosclerotic burden (e.g. by preventative strategies towards risk factors for atherosclerosis or by administration of statins) or on the inhibition of coagulation activation (e.g. by anticoagulants or anti-platelet agents). Besides these strategies, which have indeed been proven to be effective, stabilization of the atherosclerotic plaque could theoretically prevent plaque rupture and its … *Corresponding author. Tel: +31 20 5662171; fax: +31 20 6919658. E-mail address : m.m.levi{at}amc.uva.nl