Prevention of LDL α-tocopherol consumption, cholesterol oxidation, and vascular endothelium dysfunction by polyphenolic compounds from red wine

Abstract

Red wine polyphenolic compounds (RWPCs) have been demonstrated to possess antioxidant properties, and several studies have suggested that they might constitute a relevant dietary factor in the protection from coronary heart disease. The aim of the present study was to determine further the mechanism by which RWPCs can prevent the formation of vasoactive compounds in oxidized LDL. RWPCs were obtained from the Cabernet-Sauvignon grape variety. Human LDL was oxidized in the presence of CuSO 4 (ox-LDL). Vascular reactivity studies were conducted on rabbit aortic rings. RWPCs significantly reduced the formation of 7β-hydroxycholesterol and 7-ketocholesterol and in a lower extent the emergence of lysophosphatidylcholine in ox-LDL. The ability of RWPCs to prevent cholesterol oxide formation was directly dependent on the LDL α-tocopherol content. Once the LDL α-tocopherol has been consumed, RWPCs were no longer effective, indicating that RWPCs act by sparing endogenous α-tocopherol. As a consequence of the preservation of the endogenous α-tocopherol content of LDL, RWPCs could prevent the inhibition of the acetylcholine-mediated endothelium-dependent relaxation of rabbit aorta which was linked to a direct effect on NO release. Independently of a treatment with ox-LDL, RWPC exerted a concentration-dependent and persistent inhibitory effect on the norepinephrine-induced contraction of rabbit aorta. In conclusion, RWPCs can preserve a normal vascular reactivity by acting at different stages of the cascade that leads to lipid oxidation, endothelium dysfunction and vasospasm.