Abstract

Hypercholesterolemia, and in particular high levels of low density lipoprotein (LDL), is a well established risk factor for development of coronary heart disease (CHD), but the biological mechanisms by which LDL promote formation of atherosclerotic plaques are still poorly understood. During the last decade several lines of evidence have suggested that oxidative modification of LDL is a key process in this respect. Oxidation of LDL has been found to increase its uptake in macrophages and lead to formation of macrophage foam cells. Other studies have indicated that oxidized LDL may induce vascular inflammation and even give rise to autoimmune reactions in the vascular wall. These findings have it made important to investigate the possible role of LDL oxidation in CHD also in clinical studies and the initial results of such studies support the notion that oxidation of LDL also may be of clinical relevance. In a group of young post-myocardial infarction patients the in vitro susceptibility of LDL to oxidative modification was found to be significantly related to the severity of coronary atherosclerosis as assessed by angiography. In another study presence of antibodies against oxidized LDL was found to be associated with increased progression of carotid disease. Should these findings be confirmed in larger patient groups and LDL oxidation established as a key factor in the development of atherosclerosis this would have a considerable impact on future strategies for prevention and treatment of coronary heart disease.