Reduced cardiac expression of plasminogen activator inhibitor 1 and transforming growth factor beta1 in obese Zucker rats by perindopril.
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.
Toblli
J E
JE
Laboratory of Experimental Medicine, Hospital Alemán, CONICET, Av Pueyrredon 1640, Buenos Aires 1118, Argentina. jtoblli@hospitalaleman.com
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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
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