363 BLOCKING OF PROFIBROGENIC FACTOR TRANSFORMING GROWTH FACTOR β BLUNTED THE PRESSURE OVERLOAD-INDUCED CARDIAC INTERSTITIAL FIBROSIS AND REMODELING. (1st January 2005) - Mehta, N.
Abstract : Background: We have shown enhanced expression of transforming growth factor (TGF)- β1 and collagen in heart in response to pressure overload stress induced by transverse aortic constriction (TAC). Hypothesis: Cardiac fibrosis/remodeling in response to TAC is blunted in dominant negative TGF-β receptor II (DnTGFβRII) mice in which the profibrogenic effect of TGF-β is blocked. Method: Adult male DnTGFβRII and wild-type nontransgenic (NTG) mice were given 25 mM ZnSO4 in their drinking water for 2 weeks prior to TAC or sham surgery in order to induce DnTGFβ type II receptor expression. One week later, echocardiogram was done to evaluate heart function and then hearts were weighed and analyzed for collagen content. Collagen volume percent in the interstitial and perivascular regions of the left ventricle (LV) was measured using picrosirius red staining. Results and Conclusion: Cardiac hypertrophy, with unchanged heart function, developed in both DnTGFβRII and NTG mice 1 week post TAC. The TAC-induced cardiac hypertrophy was accompanied by an increase in collagen volume in the interstitial space of NTG, but not DnTGFβRII mice. Interestingly, the TAC-induced perivascular collagen deposition in response to pressure overload stress was exaggerated in DnTGFβRII mice. These findings(figure ) support our hypothesis that TGF-β is an important modulator of extracellular matrix expression and cardiac remodeling in response to pressure overload stress.