Plaque rupture, thrombosis, and therapeutic implications

Abstract

The basic mechanisms of atherosclerotic progression leading to the acute coronary syndromes (ACS) have been elucidated during the last few years. In this brief presentation, we outline 1) Definition of Atherosclerotic Lesions: eight morphologically different lesions are defined (Type I to VI) in various phases of disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type IV and Va lesions tend to be relatively small in size, but soft or vulnerable to a "passive" phenomenon of plaque disruption; in addition, an "active" macrophage-dependent enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich plaques may play a detrimental role after plaque disruption, promoting thrombin generation and thrombosis through the tissue factor pathway that can be prevented by tissue factor pathway inhibition; such pathway of thrombosis appears to be critical in the development of the ACS. 4) Effect of Lipid-Modifying Strategies and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the liquid or sterified cholesterol, and also its hydrolysis into cholesterol crystals depositing in the vessel wall, predominate over the influx of LDL-cholesterol; consequently, there is a decrease in the softness of the plaque and so, presumably in the "passive" phenomenon of plaque disruption; modification of other risk factors presumably also favorably affect LDL-cholesterol influx and efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches under investigation are briefly outlined.