Sodium hydrosulfide prevents myocardial dysfunction through modulation of extracellular matrix accumulation and vascular density

• Published in: International journal of molecular sciences 2014-12, Vol.15 (12), p.23212-23226
• Main Authors: Pan, Li-Long, Wang, Xian-Li, Wang, Xi-Ling, Zhu, Yi-Zhun
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Animals; cardioprotection; Cellular biology; Collagen Type II - genetics; Collagen Type II - metabolism; Collagen Type III - genetics; Collagen Type III - metabolism; Cystathionine gamma-Lyase - genetics; Cystathionine gamma-Lyase - metabolism; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Fibrosis - metabolism; Heart attacks; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hydrogen sulfide; infarction; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; neovascularization; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; remodeling; Sulfides - pharmacology; Sulfides - therapeutic use; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Ventricular Remodeling
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms151223212

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.