title: Angiotensin-converting enzyme-2 overexpression improves atrial remodeling and function in a canine model of atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrosis is an important factor in initiating and maintaining atrial fibrillation. The purpose of this study was to test the hypothesis that atrial angiotensin-converting enzyme-2 (ACE2) overexpression might inhibit atrial collagen accumulation and improve atrial remodeling in a canine atrial pacing model.
  
  
  RESULTS
  Thirty-two mongrel dogs of both genders were divided randomly into 4 groups: sham-operated, control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP), and gene therapy with Ad-ACE2. All of the dogs in the control, Ad-EGFP, and Ad-ACE2 groups were paced at 450 bpm for a period of 14 days. The dogs in the sham group were instrumented without pacing. After 2 weeks, all of the dogs underwent a thoracotomy operation and received epicardial gene painting. On post-gene transfer day 21, the animals underwent electrophysiology, histology, and molecular studies. The percentage of fibrosis in the Ad-ACE2 group was markedly lower than the percentage in the control and Ad-EGFP groups. Compared with the other groups, ACE2 expression was increased significantly in the Ad-ACE2 group. Compared with the sham and Ad-ACE2 groups, the expression levels of transforming growth factor-β1 and Smad3 were significantly higher in the Ad-EGFP and control groups; however, the expression levels of Smad7 were lower in the atrial tissue as detected by Western blot and reverse transcription polymerase chain reaction.
  
  
  CONCLUSIONS
  Our results demonstrate that the overexpression of ACE2 inhibits atrial collagen accumulation and improves left atrial remodeling and function in a canine model of atrial fibrillation. Thus, targeted gene ACE2 therapy provides a promising approach for the treatment of atrial fibrillation.
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Tingquan
authors: T
authors: Zhou
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Zhenglong
authors: Z
authors: Wang
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Jinqi
authors: J
authors: Fan
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Shaojie
authors: S
authors: Chen
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Zhen
authors: Z
authors: Tan
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Hanxuan
authors: H
authors: Yang
authors: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (T.Z., Z.W., J.F., S.C., Z.T., H.Y., Y.Y.).
authors: Yuehui
authors: Y
authors: Yin
mesh_terms: D000200:Action Potentials; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001281:Atrial Fibrillation / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016279:Atrial Function, Left; D064752:Atrial Remodeling; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004285:Dogs; D004790:Enzyme Induction; D005260:Female; D005355:Fibrosis; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006325:Heart Atria / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D020127:Recovery of Function; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2
keywords: angiotensin II; angiotensin‐converting enzyme 2; atrial fibrillation; atrial fibrosis; extracellular matrix; transforming growth factor‐β1