The study was designed to explore the role and possible mechanisms of hydrogen sulfide (H2S) in the regulation of myocardial collagen remodeling in spontaneously hypertensive rats (SHRs). We treated nine-week-old male SHRs and age- and sex-matched Wistar-Kyoto rats (WKYs) with NaHS (90 µmol/kg−1-day−1) for 9 wks. At 18 wks, plasma H2S, tail arterial pressure, morphology of the heart, myocardial ultrastructure and collagen volume fraction (CVF), myocardial expressions of collagen I and III protein and procollagen I and III mRNA, transforming growth factor-β1 (TGF-β1), TGF-β type I receptor (TβR-I), type II receptor (TβR-II), p-Smad2 and 3, matrix metalloproteinase (MMP)-13 and tissue inhibitors of MMP (TIMP)-1 proteins were determined. TGF-β 1-stimulated cultured cardiac fibroblasts (CFs) were used to further study the mechanisms. The results showed that compared with WKYs, SHRs showed a reduced plasma H2S, elevated tail artery pressure and increased myocardial collagen, TGF-β1, TβR-II, p-Smad2 and p-Smad3 expressions. However, NaHS markedly decreased tail artery pressure and inhibited myocardial collagen, TGF-β1, TβR-II, p-Smad2 and p-Smad3 protein expressions, but H2S had no effect on the expressions of MMP-13 and TIMP-1. Hydralazine reduced blood pressure but had no effect on myocardial collagen, MMP-13 and TIMP-1 expressions and TGF-β1/Smad signaling pathway. H2S prevented activation of the TGF-β1/Smad signaling pathway and abnormal collagen synthesis in CFs. In conclusion, the results suggested that H2S could prevent myocardial collagen remodeling in SHR. The mechanism might be associated with inhibition of collagen synthesis via TGF-β1/Smad signaling pathway.
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This work was supported by the Major Basic Research Development Program of People’s Republic of China (2012CB517806, 2013CB933801 and 2011CB503904), National Natural Science Foundation of China (31130030, 81370154, 81100181 and 81121061), Beijing Natural Science Foundation (7122184 and 7121014) and The Open Project of Key Laboratory of Remodelingrelated Cardiovascular Diseases, Ministry of Education (2014XXGB02).
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1.Department of Emergency MedicineBeijing Jishuitan HospitalBeijingChina
2.Department of PediatricsPeking University First HospitalBeijingChina
3.Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel DiseasesBeijing An Zhen Hospital, Capital Medical UniversityBeijingChina
4.Department of Physiology and PathophysiologyPeking University Health Science CenterBeijingChina
5.Key Laboratory of Molecular Cardiovascular SciencesMinistry of EducationBeijingChina