[LOX-1 receptor as a novel target in endothelial dysfunction and atherosclerosis].

Atherosclerosis with its complications like heart attack and stroke, is the most frequent cause of death in the industrialized countries. Oxidized low-density lipoproteins (LDL) play a major role in the pathogenesis of atherosclerosis. Inhibition of cholesterol synthesis by statins has several protective effects but is not sufficient to prevent the uptake of oxidized LDL and the development of atherosclerotic plaques. For this reason a selective pharmacological inhibition of the uptake of oxidized LDL (oxLDL) in endothelial cells is an interesting therapeutic approach. An important novel target molecule is the endothelial lectin-like oxLDL receptor LOX-1. This receptor is able to take up both minimally and highly oxidized LDL. In addition it mediates endothelial phagocytosis of aged and apoptotic cells and plays a role in thrombocyte adhesion and in the interaction between bacterial proteins and endothelial cells in sepsis. LOX-1 is induced by proinflammatory cytokines, oxLDL, angiotensin II, endothelin-1 and arterial hypertension. LOX-1 increases endothelial dysfunction and atherosclerosis by endothelial uptake of oxLDL. This is the reason why LOX-1 has been considered as a novel link between hypertension and atherosclerosis. Transgenic overexpression of the LOX-1 receptor and high-fat diet induces intramyocardial vascular disease and endothelial dysfunction in resistance arteries. In contrast, genetic deletion of the LOX-1 gene reduces the development of atherosclerotic plaques. In the clinical context LOX-1 has been detected in the early phase of endothelial dysfunction and atherosclerosis in arteries of patients with coronary heart disease. Several novel data support a role of LOX-1 in the endothelial dysfunction in diabetic vascular and renal disease, hypercholesterolemia, obesity and preeclampsia. This makes the LOX-1 receptor a novel and interesting target molecule in endothelial dysfunction and atherosclerosis. Georg Thieme Verlag KG Stuttgart, New York.