LPC IN OXIDIZED LDL ELICITS VASOCONTRACTION AND INHIBITS ENDOTHELIUM-DEPENDENT RELAXATION

Oxidized low-density lipoprotein (ox-LDL) plays an important role in the development of atherosclerosis and potentially influences the endothelial regulation of vasomotor tone. We have recently shown that lysophosphatidylcholine (LPC), a lysophospholipid contained in ox-LDL, has various pathophysiological effects. We further examined the role of LPC in the ox-LDL-induced vasoactivity in isolated pig coronary arteries. Copper-induced ox-LDL but not native LDL (n-LDL) elicited endothelium-dependent contraction during plateau contraction evoked by prostaglandin F-2 alpha. Lipid extracted from ox-LDL (ox-LDL-lipid) also induced vasocontraction, but lipid of n-LDL (n-LDL-lipid) did not influence tone. When LPC was depleted from ox-LDL (i.e., defatted albumin- or phospholipase B-treated ox-LDL), vasocontraction was significantly attenuated. Synthetic palmitoyl LPC also induced endothelium-dependent vasocontraction, mimicking the response elicited by ox-LDL, but phosphatidylcholine, which exists in n-LDL and is converted to LPC during oxidative modification of LDL, did not influence the tone. Contraction to either ox-LDL or LPC was significantly attenuated by N-G-monomethyl-L-arginine but not by indomethacin or superoxide dismutase. Forty minutes of incubation of coronary rings with either ox-LDL or LPC significantly attenuated endothelium-dependent vasorelaxation to thrombin without affecting vasorelaxation to endothelium-independent vasodilator nitroglycerin. In conclusion, LPC contained in lipid fraction of ox-LDL caused endothelium-dependent contraction and inhibited endothelium-dependent relaxation in isolated pig coronary arteries. The vasocontraction might be at least in part caused by LPC-mediated inhibition of endothelium-derived nitric oxide release. This vasoactive property of LPC may be attributable to ox-LDL-induced alteration of vasomotor regulation.