title: Growth/differentiation factor 1 alleviates pressure overload-induced cardiac hypertrophy and dysfunction.
abstract: Pathological cardiac hypertrophy is a major risk factor for developing heart failure, the leading cause of death in the world. Growth/differentiation factor 1 (GDF1), a transforming growth factor-β family member, is a regulator of cell growth and differentiation in both embryonic and adult tissues. Evidence from human and animal studies suggests that GDF1 may play an important role in cardiac physiology and pathology. However, a critical role for GDF1 in cardiac remodelling has not been investigated. Here, we performed gain-of-function and loss-of-function studies using cardiac-specific GDF1 knockout mice and transgenic mice to determine the role of GDF1 in pathological cardiac hypertrophy, which was induced by aortic banding (AB). The extent of cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. Our results demonstrated that cardiac specific GDF1 overexpression in the heart markedly attenuated cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas loss of GDF1 in cardiomyocytes exaggerated the pathological cardiac hypertrophy and dysfunction in response to pressure overload. Mechanistically, we revealed that the cardioprotective effect of GDF1 on cardiac remodeling was associated with the inhibition of the MEK-ERK1/2 and Smad signaling cascades. Collectively, our data suggest that GDF1 plays a protective role in cardiac remodeling via the negative regulation of the MEK-ERK1/2 and Smad signaling pathways.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China.
authors.forename: Ding-Sheng
authors.initials: DS
authors.lastname: Jiang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360, USA.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China; Departments of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Guo-Chang
authors.initials: GC
authors.lastname: Fan
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China. Electronic address: huangcongxin@vip.163.com.
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D006332:Cardiomegaly / Q000235:genetics / Q000503:physiopathology*; D002478:Cells, Cultured; D055452:Growth Differentiation Factor 1 / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D055452:Growth Differentiation Factor 1; D051899:Smad2 Protein; D051900:Smad3 Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1
keywords: Cardiac hypertrophy; ERK1/2; Fibrosis; GDF1; Smad