Supression of hemin-mediated oxidation of low-density lipoprotein and subsequent endothelial reactions by hydrogen sulfide (H2S)

Jeney, Viktória and Komódi, E. and Nagy, E. and Zarjou, A. and Vercellotti, G.M. and Balla, György and Balla, József (2009) Supression of hemin-mediated oxidation of low-density lipoprotein and subsequent endothelial reactions by hydrogen sulfide (H2S). FREE RADICAL BIOLOGY AND MEDICINE, 46 (5). pp. 616-623. ISSN 0891-5849

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Abstract

Heme-mediated oxidative modification of low-density lipoprotein (LDL) plays a crucial role in early atherogenesis. It has been shown that hydrogen sulfide (H2S) produced by vascular smooth muscle cells is present in plasma at a concentration of about 50 mu mol/L. H2S is a strong reductant which can react with reactive oxygen species like superoxide anion and hydrogen peroxide. The current study investigated the effect of H2S on hemin-mediated oxidation of LDL and oxidized LDL (oxLDL)-induced endothelial reactions. H2S dose dependently delayed the accumulation of lipid peroxidation products-conjugated dienes, lipid hydroperoxides (LOOH), and thiobarbituric acid reactive substances-during hemin-mediated oxidation. Moreover, H2S decreased the LOOH content of both oxidized LDL and lipid extracts derived from soft atherosclerotic plaque, which was accompanied by reduced cytotoxicity. OxLDL-mediated induction of the oxidative stress responsive gene, heme oxygenase-1, was also abolished by H2S. Finally we have shown that H2S can directly protect endothelium against hydrogen peroxide and oxLDL-mediated endothelial cytotoxicity. These results demonstrate novel functions of H2S in preventing hemin-mediated oxidative modification of LDL, and consequent deleterious effects, suggesting a possible antiatherogenic action of H2S. (C) 2008 Elsevier Inc. All rights reserved.

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