title: Angiotensin-converting enzyme-2 overexpression improves left ventricular remodeling and function in a rat model of diabetic cardiomyopathy.
abstract: OBJECTIVE
  The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular (LV) remodeling and function in diabetic cardiomyopathy.
  
  
  BACKGROUND
  Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction.
  
  
  METHODS
  Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus-enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase-2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection.
  
  
  RESULTS
  Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase-2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus-enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor-beta production and enhanced collagen degradation by matrix metalloproteinase-2.
  
  
  CONCLUSIONS
  ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dong
authors.forename: Qing Tao
authors.initials: QT
authors.lastname: Yu
authors.forename: Hong Yan
authors.initials: HY
authors.lastname: Dai
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Gao
authors.forename: Zhao Li
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Shu Ying
authors.initials: SY
authors.lastname: Li
authors.forename: Yue Hui
authors.initials: YH
authors.lastname: Zhang
authors.forename: Hong Jun
authors.initials: HJ
authors.lastname: Bian
authors.forename: Chun Xi
authors.initials: CX
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Chun Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Huai Dong
authors.initials: HD
authors.lastname: Song
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental; D058065:Diabetic Cardiomyopathies / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D004452:Echocardiography; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2