REGULATION OF MESSENGER-RNA TRANSCRIPTS AND DNA-SYNTHESIS IN THE RAT-HEART FOLLOWING INTRAVENOUS-INJECTION OF TRANSFORMING GROWTH-FACTOR BETA(1)

Transforming Growth Factor-beta(1) (TGF-beta(1)) is expressed in the h eart by muscle and non-muscle cardiac cells. In vitro, cardiac myocyte s and non-muscle cells including cardiac fibroblasts and endothelial c ells respond to regulatory effects of TGF-beta(1). Expression of TGF-b eta(1) in the heart is subject to regulation by hemodynamic stimuli. I ncreased expression of mRNA transcripts for TGF-beta(1) has been repor ted in several models of cardiac hypertrophy. The objective of this st udy was to determine the effect of TGF-beta(1) in the myocardium. TGF- beta(1) was injected intravenously. Expression of mRNA transcripts for functional and structural proteins was determined by Northern hybridi zation analysis. DNA synthesis was determined by measurement of H-3-th ymidine incorporation into ventricular DNA. The results showed differe ntial regulation of mRNAs for myocyte- and non-myocyte-specific protei ns in the heart of TGF-beta(1) treated rats. Moderate but statisticall y significant decrease in DNA synthesis was observed in the heart of T GF-beta(1) treated rats (37.5%, P<0.025). Together, these data point t o a physiological role for TGF-beta(1) in the heart. They further sugg est that similar to its diverse in vitro cell-specific regulatory effe cts, TGF-beta(1) may have multicellular targets in the heart. Effect o f TGF-beta(1) alone or combined with those of other cytokines/hormones that come into play as the result of its administration, may be respo nsible for altered gene expression and DNA synthesis in the myocardium . We propose that in experimental models of myocardial hypertrophy whi ch are associated with increased expression of TGF-beta(1) in the hear t, the contribution of regulatory effects of this growth factor to the manifestations of ventricular hypertrophy could be significant.