title: Reduced cardiac expression of plasminogen activator inhibitor 1 and transforming growth factor beta1 in obese Zucker rats by perindopril.
abstract: OBJECTIVE
  To determine whether angiotensin converting enzyme inhibition by perindopril can reduce cardiac transforming growth factor beta1 (TGFbeta1) and plasminogen activator inhibitor 1 (PAI-1) and therefore control collagen accumulation in an animal model with the metabolic syndrome such as the obese Zucker rat (OZR).
  
  
  METHODS
  Male OZR (group 1, n = 10); OZR treated with perindopril (group 2, n = 10); and lean Zucker rats (group 3, n = 10).
  
  
  METHODS
  During six months, group 2 received 3 mg/kg/day of perindopril orally and group 1 and group 3 were given a vehicle. Hearts were processed for pathology studies including immunohistochemical analysis with antibodies to PAI-1, TGFbeta1, collagen type I, and collagen type III.
  
  
  RESULTS
  Group 2 had lower blood pressure (126.7 (2) v 148.6 (2.7) mm Hg, p < 0.01) than untreated OZR and had decreased cardiac PAI-1 (3.6 (0.4) v 13.5 (1.7)% of positive area/field, p < 0.01), TGFbeta1 in myocytes (0.13 (0.1) v 9.14 (4.7)%/area, p < 0.01) and in interstitium (19.8 (6.8) v 178.9 (27.4) positive cells/area, p < 0.01), collagen I (3 (0.8) v 13.3 (1)%/area, p < 0.01), collagen III (5 (0.6) v 9.5 (0.9)%/area, p < 0.01), and collagen I to collagen III ratio (0.59 (0.13) v 1.40 (0.15) p < 0.01) compared with untreated OZR.
  
  
  CONCLUSIONS
  These results suggest that perindopril reduces cardiac PAI-1 and TGFbeta1 and ameliorates cardiac fibrosis in a rat model with multiple cardiovascular risk factors.
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, CONICET, Av Pueyrredon 1640, Buenos Aires 1118, Argentina. jtoblli@hospitalaleman.com
authors.forename: J E
authors.initials: JE
authors.lastname: Toblli
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.forename: G
authors.initials: G
authors.lastname: DeRosa
authors.forename: P
authors.initials: P
authors.lastname: Forcada
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D016212:Transforming Growth Factor beta / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D020913:Perindopril