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

Abstract

Heme-mediated oxidative modification of low-density lipoprotein (LDL) plays a crucial role in early atherogenesis. It has been shown that hydrogen sulfide (H(2)S) produced by vascular smooth muscle cells is present in plasma at a concentration of about 50 micromol/L. H(2)S is a strong reductant which can react with reactive oxygen species like superoxide anion and hydrogen peroxide. The current study investigated the effect of H(2)S on hemin-mediated oxidation of LDL and oxidized LDL (oxLDL)-induced endothelial reactions. H(2)S dose dependently delayed the accumulation of lipid peroxidation products-conjugated dienes, lipid hydroperoxides (LOOH), and thiobarbituric acid reactive substances-during hemin-mediated oxidation. Moreover, H(2)S 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 H(2)S. Finally we have shown that H(2)S can directly protect endothelium against hydrogen peroxide and oxLDL-mediated endothelial cytotoxicity. These results demonstrate novel functions of H(2)S in preventing hemin-mediated oxidative modification of LDL, and consequent deleterious effects, suggesting a possible antiatherogenic action of H(2)S.

Hemin-induced suicidal erythrocyte death

“…The impact of hemin-induced eryptosis on microcirculation may be compounded by effects of hemin on endothelial cells. Hemin induces oxidative stress in endothelial cells [2,18,33,34]. On the one hand, hemin-induced oxidative stress may stimulate apoptosis of nucleated cells [7,47]; on the other hand, it upregulates heme oxidase [2,15,18,30], which in turn confers resistance to apoptosis [2,30,66].…”

Role of Cystathionineγ-Lyase/Hydrogen Sulfide Pathway in Cardiovascular Disease: A Novel Therapeutic Strategy?

“…Oxidative modification of low-density lipoprotein plays a crucial role in early atherogenesis. Jeney and co-workers (26) found that H 2 S inhibited hemin-induced oxidative modification of LDL through a mechanism involving a reduction of lipid hydroperoxide content. As such, the direct or indirect modulation of intracellular ROS level by H 2 S may have important implications in the development of atherosclerosis.…”

H2S: A New Approach to Lifespan Enhancement and Healthy Ageing?

“…NaSH treatment reverses LPS (lipopolysaccharide)-induced iNOS expression and NO release Muzaffar et al 2008) and prevents homocysteine-induced toxicity and subsequent ROS formation in VSMCs (Yan et al 2006). Likewise, exogenous H 2 S attenuates oxidised low-density lipoprotein (oxLDL)-induced cytotoxicity in cultured HUVECs and was shown to protect against atherosclerosis (Laggner et al 2007a, b;Jeney et al 2009). The anti-atherosclerotic effect of H 2 S is further supported by the reported inhibition of platelet aggregation (Zagli et al 2007), inhibition of VSMCs proliferation (Du et al 2004) and reduction of neointima formation of balloon-injured carotid arteries (Meng et al 2007).…”