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 μmol/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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Free Radical Biology and Medicine|
|State||Published - Mar 1 2009|
Bibliographical noteFunding Information:
This work was supported by Hungarian Government Grants OTKA-K61546, ETT-337/2006, RET-06/2004, and MTA-DE-11003. We thank Erika Barna for technical assistance.
- Heme oxygenase-1
- Hydrogen sulfide
- Lipid hydroperoxide
- Low-density lipoprotein