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Hydrogen sulfide (H 2 S) is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H 2 S in modulating myocardial fibrosis  in vivo  and cardiac fibroblast proliferation  in vitro  remain unclear. We investigated the effect of GYY4137, a slow-releasing H 2 S 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- β 1 (TGF- β 1) 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- β 1/Smad2 signaling pathway, and decrease in  α -SMA expression in cardiac fibroblasts.

Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis