Endothelial dysfunction and dyslipidemia: possible effects of lipid lowering and lipid modifying therapy.
Hypercholesterolemic and atherosclerotic coronary endothelial dysfunction consist of a progressive, not irreversible, impairment in reactions to various endothelium dependent relaxing substances in both the epicardial coronary artery and in the resistance vessel. Paradoxical vasoconstriction, dynamic stenoses and dysregulation of the coronary blood flow make this endothelial dysfunction contribute to the pathogenesis of myocardial ischemia. The selectivity of the impairment makes the concept of specific receptor operated signal transductions in hypercholesterolemia and low doses of oxidized LDL likely. In progressive atherosclerosis and high levels of oxidized LDL the dysfunction may spread to other receptors, the availability of L-arginine may decrease and the metabolism of EDRF change. Cholesterol-lowering therapy may restore this endothelial dysfunction. This paper will discuss the recent pathophysiological insights in dyslipidemic endothelial dysfunction and exposes the mode of action of various therapeutic drugs.
van Boven
A J
AJ
Department of Cardiology, University Hospitals of Leiden, The Netherlands.
Jukema
J W
JW
Paoletti
R
R
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology*; D008074:Lipoproteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
D000924:Anticholesteremic Agents; D008074:Lipoproteins; D009569:Nitric Oxide