Mikamo Lecture

A Radical View of the `Superfamily' of Cardiovascular Risk Factors

Abstract

Many risk factors for cardiovascular disease generate superoxide in the blood vessels and thereby impair endothelial function. To emphasize the critical role of oxygen radicals, this is a `radical view' of those risk factors. It will be useful to organize risk factors into a `superfamily', with consideration of mediators, mechanisms, and target organs. Studies are summarized which suggest that, in parallel with the impairment of endothelial vasomotor function, the thrombin/thrombomodulin/activated protein C anticoagulant mechanism, which requires endothelial thrombomodulin, is also impaired by atherosclerosis and improves during regression of atherosclerosis. Impairment of the anticoagulant mechanism may contribute to thrombosis in atherosclerotic arteries, and improvement of the anticoagulant mechanism during regression of atherosclerosis may reduce the risk of cardiovascular events. (Circ J 2003; 67: 805 - 809)