Vitamin E inhibits lysophosphatidylcholine-induced endothelial dysfunction and platelet activation.

Abstract

Lysophosphatidylcholine (LPC), a lysolipid contained in oxidized low-density lipoprotein, is an atherogenic molecule that induces endothelial dysfunction and platelet activation and inhibits angiogenesis. Although studies showed that vitamin E has antiatherogenic properties, the effects of vitamin E on LPC-induced endothelial dysfunction and platelet activation are little known. We examined whether vitamin E has protecting actions against LPC-induced alterations of endothelial and platelet functions. Incubation of cultured bovine aortic endothelial cells (BAECs) with LPC (10 microM) significantly inhibited bradykinin (1 microM)-stimulated nitric oxide release, which was prevented by cotreatment with vitamin E (50, 100, and 500 microg/ml) in a concentration-dependent manner. In isolated human platelets, LPC stimulated P-selectin expression and induced leukocyte-platelet interaction, which functionally depends on P-selectin expressed on the platelet surface. Vitamin E treatment significantly prevented the LPC-induced platelet P-selectin expression and leukocyte-platelet interaction. As LPC-induced endothelial dysfunction and platelet activation have been shown to involve the protein kinase C (PKC)-dependent signal transduction pathway, we examined the effects of vitamin E on LPC-induced PKC activation in human platelets and BAECs. Vitamin E significantly inhibited LPC (10 microM)-stimulated PKC activation in a concentration-dependent manner. It is concluded that (a) Vitamin E prevented LPC-induced endothelial dysfunction and preserved endothelial nitric oxide release, (b) vitamin E inhibited LPC-induced platelet activation (P-selectin expression) and leukocyte-platelet interaction, and (c) these mechanisms appeared to be at least partly mediated by suppression of the PKC in endothelial cells and platelets. The present findings may provide new insights into antiatherogenic mechanisms of vitamin E.