Reduced cardiac expression of plasminogen activator inhibitor 1 and transforming growth factor β1 in obese Zucker rats by perindopril

Abstract

Objective: To determine whether angiotensin converting enzyme inhibition by perindopril can reduce cardiac transforming growth factor β1 (TGFβ1) 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). Animals: 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, TGFβ1, 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), TGFβ1 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. Conclusion: These results suggest that perindopril reduces cardiac PAI-1 and TGFβ1 and ameliorates cardiac fibrosis in a rat model with multiple cardiovascular risk factors.