HYPERLIPIDEMIC ENDOTHELIAL INJURY AND ANGIOGENESIS

Hypercholesterolemia is associated with endothelial cell dysfunction which may in part be related to an accumulation of toxic lipoprotein degradation products in artery walls. Oxidized low-density lipoprotein (LDL) and its products have been incriminated in impairing various endothelial functions including G-protein-dependent transmembrane signaling, calcium regulation, phosphoinositide turnover, protein kinase C activation and others. Modification of such cell regulatory functions may alter the responsiveness of endothelial cells to angiogenic (mitogenic) stimuli. Endothelial cell replication is necessary for the growth of preexisting arterial channels and the formation of new microvessels (angiogenesis). Experiments in intact rabbits indicate that endothelial replication necessary for vascular growth is markedly impaired in the presence of hypercholesterolemia, a defect that could play an important role in the pathophysiology of occlusive atherosclerotic disease.