title: 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.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China ; Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Meng
authors.affiliation: Aoyong Hospital, Zhangjiagang 215600, China.
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China ; Department of Pathology, Jincheng People's Hospital, Jincheng 048000, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Anesthesia, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Thoracic and Cardiac Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, ON, Canada P7B 5E1.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, National University of Singapore, Singapore 117597.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D000804:Angiotensin II; D024042:Collagen Type I; D024043:Collagen Type II; D006909:Hydroxyproline; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D017382:Reactive Oxygen Species; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; C529376:GYY 4137; C497784:Smad2 protein, rat; C498862:Acta2 protein, rat