INDUCTION OF HYPERTROPHIC RESPONSIVENESS TO ISOPROTERENOL BY TGF-BETAIN ADULT-RAT CARDIOMYOCYTES

In a previous publication we reported that hypertrophic responsiveness to beta-adrenoceptor stimulation can be induced in isolated cardiomyo cytes when these are cultured for 6 days in presence of fetal calf ser um (FCS; Pinson et al., J. Mob. 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 tha t induction of hypertrophic responsiveness to beta-adrenoceptor stimul ation was abolished when a neutralizing anti-TGF-beta(1) antibody was added to FCS-containing culture medium. In culture media with FCS cont ents (5%) too low to induce hypertrophic responsiveness to beta-adreno ceptor stimulation, addition of 1 ng/ml TGF-beta(1,2) induces this res ponsiveness. It was demonstrated that cardiomyocytes already release T GF-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 demonstra te that hypertrophic responsiveness to beta-adrenoceptor stimulation i s induced in cardiomyocytes by an autocrine mechanism involving TGF-be ta(1) as mediator.