HYPERTROPHIC STIMULI INDUCE TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION IN RAT VENTRICULAR MYOCYTES

Transforming growth factor-beta(1) (TGF-beta(1)) is a peptide growth f actor that may play a role in the myocardial response to hypertrophic stimuli. However, the cellular distribution, mechanism of induction, a nd source of increased TGF-beta(1) in response to hypertrophic stimuli are not known. We tested the hypothesis that the cardiac myocyte resp onds to hypertrophic stimuli with the increased expression of TGF-beta (1). In adult rat ventricular myocardium freshly dissociated into myoc yte and nonmyocyte cellular fractions, the preponderance of TGF-beta(1 ) mRNA visualized by Northern hybridization was in the nonmyocyte frac tion. Abdominal aortic constriction (7 d) and subcutaneous norepinephr ine infusion (36 h) each caused ventricular hypertrophy associated wit h 3.1-fold and 3.8-fold increases, respectively, in TGF-beta(1) mRNA i n the myocyte fraction, but had no effect on the level of TGF-beta(1) mRNA in the nonmyocyte fraction. In ventricular myocytes, norepinephri ne likewise caused a 4.1-fold increase in TGF-beta(1) mRNA associated with an increase in TGF-beta bioactivity. This induction of TGF-beta(1 ) mRNA occurred at norepinephrine concentrations as low as 1 nM and wa s blocked by prazosin, but not propranolol. NE did not increase the TG F-beta(1) mRNA level in nonmyocytes, primarily fibroblasts, cultured f rom neonatal rat ventricle. Thus, the cardiac myocyte responds to two hypertrophic stimuli, pressure overload and norepinephrine, with the i nduction of TGF-beta(1). These data support the view that TGF-beta(1), released by myocytes and acting in an autocrine and/or paracrine mann er, is involved in myocardial remodeling by hypertrophic stimuli.