title: Impairment of cardiac function and remodeling induced by myocardial infarction in rats are attenuated by the nonpeptide angiotensin-(1-7) analog AVE 0991.
abstract: OBJECTIVE
  We evaluated effects of the nonpeptide angiotensin (ANG)-(1-7) analog AVE 0991 (AVE) on cardiac function and remodeling as well as transforming growth factor-beta1 (TGF-β1)/tumor necrosis factor-alpha (TNF-α) expression in myocardial infarction rat models.
  
  
  RESULTS
  Sprague-Dawley rats underwent either sham surgery or coronary ligation. They were divided into four groups: sham, control, AVE, and AVE+A-779 [[D-Ala(7) ]-ANG-(1-7), a selective antagonist for the ANG-(1-7)] group. After 4 weeks of treatment, the AVE group displayed a significant elevation in left ventricular fractional shorting (LVFS) (25.5 ± 7.3% vs. 18.4 ± 3.3%, P < 0.05) and left ventricular ejection fraction (LVEF) (44.8 ± 7.6% vs. 32.7 ± 6.5%, P < 0.05) when compared to the control group, but no effects on the left ventricular end-diastolic and end-systolic diameters (LVDd and LVDs, respectively) were observed. In addition, we found that the myocyte diameter (18 ± 2 μm vs. 22 ± 4 μm, P < 0.05), infarct size (42.6 ± 3.6% vs. 50.9 ± 4.4%, P < 0.001) and collagen volume fraction (CVF) (16.4 ± 2.2% vs. 25.3 ± 3.2%, P < 0.001) were significantly reduced in the AVE group when compared to the control group. There were no differences in LVFS, LVEF, myocyte diameter, and infarct size between the control and AVE+A-779 groups. AVE also markedly attenuated the increased mRNA expression of collagen I (P < 0.001) and collagen III (P < 0.001) and inhibited the overexpression of TGF-β1 (P < 0.05) and TNF-α (P < 0.05) compared to the control group.
  
  
  CONCLUSIONS
  AVE could improve cardiac function and attenuate ventricular remodeling in MI rat models. It may involve the inhibition of inflammatory factors TGF-β1/TNF-α overexpression and the action on the specific receptor Mas of ANG-(1-7).
authors.affiliation: Cardiovascular Medical Department, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wu-tao
authors.initials: WT
authors.lastname: Zeng
authors.forename: Wei-yan
authors.initials: WY
authors.lastname: Chen
authors.forename: Xiu-yu
authors.initials: XY
authors.lastname: Leng
authors.forename: Li-long
authors.initials: LL
authors.lastname: Tang
authors.forename: Xiu-ting
authors.initials: XT
authors.lastname: Sun
authors.forename: Cui-ling
authors.initials: CL
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Dai
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: C092006:7-Ala-angiotensin (1-7); C469726:AVE 0991; D002316:Cardiotonic Agents; D007093:Imidazoles; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D003094:Collagen