Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis.

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H2S in modulating myocardial fibrosis in vivo and cardiac fibroblast proliferation in vitro remain unclear. We investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial fibrosis. Spontaneously hypertensive rats (SHR) were administrated with GYY4137 by intraperitoneal injection daily for 4 weeks. GYY4137 decreased systolic blood pressure and inhibited myocardial fibrosis in SHR as evidenced by improved cardiac collagen volume fraction (CVF) in the left ventricle (LV), ratio of perivascular collagen area (PVCA) to lumen area (LA) in perivascular regions, reduced hydroxyproline concentration, collagen I and III mRNA expression, and cross-linked collagen. GYY4137 also inhibited angiotensin II- (Ang II-) induced neonatal rat cardiac fibroblast proliferation, reduced the number of fibroblasts in S phase, decreased collagen I and III mRNA expression and protein synthesis, attenuated oxidative stress, and suppressed α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) expression as well as Smad2 phosphorylation. These results indicate that GYY4137 improves myocardial fibrosis perhaps by a mechanism involving inhibition of oxidative stress, blockade of the TGF-β1/Smad2 signaling pathway, and decrease in α-SMA expression in cardiac fibroblasts.

• Authors: Guoliang Meng, Jinbiao Zhu, Yujiao Xiao, Zhengrong Huang, Yuqing Zhang, Xin Tang, Liping Xie, Yu Chen, Yongfeng Shao, Albert Ferro, Rui Wang, Philip K Moore, Yong Ji
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2015 Pg. 691070 ( 2015) ISSN: 1942-0994 [Electronic] United States
• PMID: 26078813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Collagen Type I
• Collagen Type II
• GYY 4137
• Morpholines
• Organothiophosphorus Compounds
• Reactive Oxygen Species
• Smad2 Protein
• Smad2 protein, rat
• Transforming Growth Factor beta1
• smooth muscle actin, rat
• Angiotensin II
• Hydroxyproline

Topics

• Actins (metabolism)
• Angiotensin II (toxicity)
• Animals
• Blood Pressure (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Collagen Type I (genetics, metabolism)
• Collagen Type II (genetics, metabolism)
• Fibroblasts (cytology, drug effects, metabolism)
• Heart (drug effects)
• Heart Ventricles (metabolism)
• Hydroxyproline (metabolism)
• Male
• Morpholines (pharmacology)
• Myocardium (metabolism, pathology)
• Organothiophosphorus Compounds (pharmacology)
• Oxidative Stress (drug effects)
• Rats
• Rats, Inbred SHR
• Rats, Sprague-Dawley
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)