Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis

Author:

Meng Guoliang12,Zhu Jinbiao3,Xiao Yujiao14,Huang Zhengrong5,Zhang Yuqing6,Tang Xin1,Xie Liping1,Chen Yu7,Shao Yongfeng8,Ferro Albert9,Wang Rui10,Moore Philip K.11,Ji Yong1

Affiliation:

1. Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China

2. Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China

3. Aoyong Hospital, Zhangjiagang 215600, China

4. Department of Pathology, Jincheng People’s Hospital, Jincheng 048000, China

5. Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China

6. Department of Cardiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China

7. Department of Anesthesia, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

8. Department of Thoracic and Cardiac Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

9. Cardiovascular Division, Department of Clinical Pharmacology, British Heart Foundation Centre of Research Excellence, Faculty of Life Sciences and Medicine, King’s College London, London SE1 9NH, UK

10. Department of Biology, Lakehead University, Thunder Bay, ON, Canada P7B 5E1

11. Department of Pharmacology, National University of Singapore, Singapore 117597

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H2S in modulating myocardial fibrosisin vivoand cardiac fibroblast proliferationin vitroremain 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 suppressedα-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 inα-SMA expression in cardiac fibroblasts.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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