The role of thrombomodulin in atherosclerosis: from bench to bedside.

Atherosclerosis remains a leading cause of morbidity and mortality worldwide. In addition to the deposition of cholesterol in the arterial wall, inflammation, cell proliferation and migration play important roles in the pathogenesis of atherosclerosis. Thrombomodulin (TM) is a cell surface-expressed glycoprotein which is predominantly synthesized by vascular endothelial cells and a critical cofactor for thrombin-mediated activation of protein C. Activated protein C is best known for its natural anticoagulant and anti-inflammatory properties. Recent evidence has revealed that TM also has protein C- and thrombin-independent physiological function. This review summarizes recent investigations of TM, giving an overview on the TM unique effects on cellular proliferation, adhesion and inflammation, all of which are important steps in atherosclerosis. The current evidence of TM in the pathogenesis of atherosclerosis will be reviewed, and the associations of TM gene polymorphisms with atherosclerosis are presented. Newly emerging data of the TM in mouse atherosclerosis model demonstrates that TM potentially may have therapeutic role in atherosclerosis.