Arteriosclerosis and Thrombosis, Vol 14, 1007-1013, Copyright © 1994 by American Heart Association

ARTICLES

Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation

Y Ohara, TE Peterson, B Zheng, JF Kuo and DG Harrison
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322.

We tested the hypothesis that lysophosphatidylcholine (lyso-PC) could activate protein kinase C in intact vascular segments and sought to examine some of the physiological consequences of this activation. In segments of rabbit aorta, the patterns of protein phosphorylation determined by two-dimensional electrophoresis stimulated by lyso-PC and 12-O-tetradecanoylphorbol 13-acetate (TPA) were similar. Activation of protein kinase C can stimulate superoxide anion (O2-) production in other tissues, and we found that lyso-PC-treated rabbit aortas produced twofold more O2- than control vessels. Calphostin C, a potent and specific inhibitor of protein kinase C, attenuated O2- production in lyso-PC-treated vessels but had no effect in control vessels. The effect of lyso-PC on O2- production was mimicked by TPA. In separate bioassay studies, release of the endothelium-derived vascular relaxing factor (EDRF) quantified by the response of detector vessels was markedly impaired after exposure of donor rabbit aortic segments to lyso-PC. After incubation with calphostin C, EDRF release in response to acetylcholine from lyso-PC-treated donor vessels was restored significantly. Thus, lyso-PC can activate protein kinase C in intact vessels, leading to an increase in O2- production. Activation of protein kinase C by lyso-PC may also play a role in altering the release of EDRF in response to acetylcholine. Increased O2- production in response to lyso-PC may have important consequences in the atherogenic process.

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