title: CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats.
abstract: Oxidative stress, inflammation and cell death are closely involved in the development of diabetic cardiomyopathy (DCM). C1q/tumour necrosis factor-related protein-3 (CTRP3) has anti-inflammatory properties but its role in DCM remains largely unknown. The aims of this study were to determine whether CTRP3 could attenuate DCM and to clarify the underlying mechanisms.
  
  
  
  Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in Sprague-Dawley rats. Cardiomyocyte-specific CTRP3 overexpression was achieved using an adeno-associated virus system 12 weeks after STZ injection.
  
  
  
  CTRP3 expression was significantly decreased in diabetic rat hearts. Knockdown of CTRP3 in cardiomyocytes at baseline resulted in increased oxidative injury, inflammation and apoptosis in vitro. Cardiomyocyte-specific overexpression of CTRP3 decreased oxidative stress and inflammation, attenuated myocyte death and improved cardiac function in rats treated with STZ. CTRP3 significantly activated AMP-activated protein kinase α (AMPKα) and Akt (protein kinase B) in H9c2 cells. CTRP3 protected against high-glucose-induced oxidative stress, inflammation and apoptosis in vitro. AMPKα deficiency abolished the protective effects of CTRP3 in vitro and in vivo. Furthermore, we found that CTRP3 activated AMPKα via the cAMP-exchange protein directly activated by cAMP (EPAC)-mitogen-activated protein kinase kinase (MEK) pathway.
  
  
  
  CTRP3 protected against DCM via activation of the AMPKα pathway. CTRP3 has therapeutic potential for the treatment of DCM.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Zhen-Guo
authors.initials: ZG
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Si-Chi
authors.initials: SC
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Chun-Ru
authors.initials: CR
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Hai-Han
authors.initials: HH
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China. qztang@whu.edu.cn.|Cardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China. qztang@whu.edu.cn.|Hubei Key Laboratory of Cardiology, Wuhan, People's Republic of China. qztang@whu.edu.cn.|Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Hubei Key Laboratory of Cardiology, Wuhan University, Jiefang Road 238, Wuhan, 430060, People's Republic of China. qztang@whu.edu.cn.
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D054392:Adipokines; C000590534:C1q tumor necrosis factor-related protein 3, rat; D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases
keywords: AMP­activated protein kinase α; Apoptosis; C1q/tumour necrosis factor-related protein-3; CTRP3; Diabetic cardiomyopathy; Inflammation; Oxidative stress