Induction of hypertrophic responsiveness to isoproterenol by TGF-beta in adult rat cardiomyocytes.

In a previous publication we reported that hypertrophic responsiveness to beta-adrenoceptor stimulation can be induced in isolated cardiomyocytes when these are cultured for 6 days in presence of fetal calf serum (FCS; Pinson et al., J. Mol. Cell. Cardiol.. 25: 477-490, 1993). The role of transforming growth factor-beta (TGF-beta) in this induction process has now been investigated. Isolated cardiomyocytes from adult rats were cultured for 6 days in presence of 20% FCS. It was found that induction of hypertrophic responsiveness to beta-adrenoceptor stimulation was abolished when a neutralizing anti-TGF-beta 1 antibody was added to FCS-containing culture medium. In culture media with FCS contents (5%) too low to induce hypertrophic responsiveness to beta-adrenoceptor stimulation, addition of 1 ng/ml TGF-beta 1,2 induces this responsiveness. It was demonstrated that cardiomyocytes already release TGF-beta into culture media on day 1 of culture and that they continue to do so in presence of FCS supplements of > 5%. The results demonstrate that hypertrophic responsiveness to beta-adrenoceptor stimulation is induced in cardiomyocytes by an autocrine mechanism involving TGF-beta 1 as mediator.