title: Sodium hydrosulfide prevents myocardial dysfunction through modulation of extracellular matrix accumulation and vascular density.
abstract: The aim was to examine the role of exogenous hydrogen sulfide (H2S) on cardiac remodeling in post-myocardial infarction (MI) rats. MI was induced in rats by ligation of coronary artery. After treatment with sodium hydrosulfide (NaHS, an exogenous H2S donor, 56 μM/kg·day) for 42 days, the effects of NaHS on left ventricular morphometric features, echocardiographic parameters, heme oxygenase-1 (HO-1), matrix metalloproteinases-9 (MMP-9), type I and type III collagen, vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in the border zone of infarct area were analyzed to elucidate the protective mechanisms of exogenous H2S on cardiac function and fibrosis. Forty-two days post MI, NaHS-treatment resulted in a decrease in myocardial fibrotic area in association with decreased levels of type I, type III collagen and MMP-9 and improved cardiac function. Meanwhile, NaHS administration significantly increased cystathionine γ-lyase (CSE), HO-1, α-SMA, and VEGF expression. This effect was accompanied by an increase in vascular density in the border zone of infarcted myocardium. Our results provided the strong evidences that exogenous H2S prevented cardiac remodeling, at least in part, through inhibition of extracellular matrix accumulation and increase in vascular density.
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. panlilong@fudan.edu.cn.
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Pan
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. 072103177@fudan.edu.cn.
authors.forename: Xian-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. 072103177@fudan.edu.cn.
authors.forename: Xi-Ling
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. zhuyz@fudan.edu.cn.
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D000199:Actins; D024043:Collagen Type II; D024061:Collagen Type III; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; D051547:Heme Oxygenase-1; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide