Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction In Atherosclerotic Lesion

Potor, László and Méhes, Gábor and Hendrik, Zoltán and Jeney, Viktória and Pethő, Dávid and Varga-Vasas, Anita and Pálinkás, Zoltán and Balogh, Enikő and Nagy, Péter and Balla, György and Balla, József (2018) Hydrogen Sulfide Abrogates Hemoglobin-Lipid Interaction In Atherosclerotic Lesion. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018. p. 3812568. ISSN 1942-0900

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Abstract

The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion hemoglobin (Hb) is oxidized to ferri- and ferrylHb which exhibit pro-oxidant and pro-inflammatory activities. Cystathione-gamma lyase (CSE)-derived H2S has been suggested to possess various anti-atherogenic actions.Expression of CSE was upregulated predominantly in macrophages, foam cells and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. Similar pattern was observed in aortic lesions of apolipoprotein E deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-? and interleukin-1?. In the interplay between hemoglobin and atheroma lipids, H2S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H2S inhibited heme and Hb-mediated lipid oxidation of human atheroma derived lipid and human complicated lesion.Our study suggests that the CSE/H2S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque.

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