%0 Journal Article
%T Chronic NaHS Treatment Is Vasoprotective in High-Fat-Fed ApoE£¿/£¿ Mice
%A Asha Ford
%A Mohammad Al-Magableh
%A Tracey A. Gaspari
%A Joanne L. Hart
%J International Journal of Vascular Medicine
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/915983
%X Hydrogen sulfide is emerging as an important mediator of vascular function that has antioxidant and cytoprotective effects. The aim of this study was to investigate the role of endogenous H2S and the effect of chronic exogenous H2S treatment on vascular function during the progression of atherosclerotic disease. ApoE£¿/£¿ mice were fed a high-fat diet for 16 weeks and treated with the H2S donor NaHS or the cystathionine-¦Ã-lyase (CSE) inhibitor D,L-propargylglycine (PPG), to inhibit endogenous H2S production for the final 4 weeks. Fat-fed ApoE£¿/£¿ mice displayed significant aortic atherosclerotic lesions and significantly impaired endothelial function compared to wild-type mice. Importantly, 4 weeks of NaHS treatment significantly reduced vascular dysfunction and inhibited vascular superoxide generation. NaHS treatment significantly reduced the area of aortic atherosclerotic lesions and attenuated systolic blood pressure. Interestingly, inhibiting endogenous, CSE-dependent H2S production with PPG did not exacerbate the deleterious vascular changes seen in the untreated fat-fed ApoE£¿/£¿ mice. The results indicate NaHS can improve vascular function by reducing vascular superoxide generation and impairing atherosclerotic lesion development. Endogenous H2S production via CSE is insufficient to counter the atherogenic effects seen in this model; however exogenous H2S treatment has a significant vasoprotective effect. 1. Introduction Hydrogen sulfide is a recently identified gasotransmitter reported to have numerous physiological effects in diverse processes including metabolism, inflammation, the nervous system, and the cardiovascular system [1]. The cardiovascular effects of this molecule are currently of major interest and include vascular relaxation, cardioprotection, and vasculoprotective effects [2, 3]. In mammalian cells, H2S is produced primarily by 2 pyridoxyl-5¡ä-phosphate-dependent enzymes, cystathionine-¦Â-synthase (CBS), and cystathionine-¦Ã-lyase (CSE). Additionally, a role for 3-mercaptopyruvate sulfurtransferase in concert with cysteine aminotransferase has been identified in the vasculature [4]. With respect to vasoregulation, CSE is of particular interest as it is reported to be present in a range of vascular beds and its expression has been clearly identified in vascular smooth muscle cells. CSE has also been located in endothelial cells and additionally it is reported to contribute to endothelium-dependent vasorelaxation [5, 6]. Inhibition of CSE with the irreversible inhibitor D,L-propargylglycine (PPG) leads to an elevation of blood pressure in
%U http://www.hindawi.com/journals/ijvm/2013/915983/