Differential protein expression and subcellular distribution of TGF beta(1), beta(2), and beta(3) in cardiomyocytes during pressure overload induced hypertrophy

The transforming growth factor beta (TGF beta) superfamily plays an important role in the myocardial response to hypertrophy. We have investigated the protein expression of TGF beta(1), beta(2) and beta(3) in left ventricular tissue, and determined their subcellular distribution in myocytes by immunoblotting and immunocytochemistry during the development of left ventricular hypertrophy (LVH), using isoform specific antibodies to TGF beta(1), beta(2) and beta(3). LVH was produced in rats by aortic constriction (AC) and LV tissue was obtained at days (d)0, 1, 3, 7, 14, 21 and 42 following operation. Compared with age matched sham-operated controls (SH), TGF beta(1) levels in LV tissue of AC rats increased significantly from d1-d14 (P<0.03) concomitant with the adaptive growth of LV tissue. In contrast, TGF beta(3) levels decreased in LV tissue of AC rats from d3 post-operation (significant from d14-d42, P<0.03). No significant difference in TGF beta(2) levels were observed from SH and AC rats after operation. Antibodies to TGF beta(1) stained intercalated disks, sarcolemmal membranes and cytoplasm, but not nuclei, of cardiomyocytes on LV sections from untreated and SH rats. However, a trans-localisation of TGF beta(1) to the nuclei of cardiomyocytes was observed in AC hearts. Antibodies to TGF beta(3) stained T tubules, cytoplasm and the nuclei of cardiomyocytes from untreated and SH rats. However, by d7 post-AC operation, TGF beta(3) expression was lost rapidly from nuclei of cardiomyocytes followed by a reduction in total TGF beta(3) immunofluorescence in myocytes. Antibodies to TGF beta(2) stained sarcolemmal membranes of cardiomyocytes from both SH and AC rats without significant difference between groups. Thus, the differential pattern of protein expression and subcellular distribution of TGF beta(1), beta(2) and beta(3) in myocytes during the development of LVH suggests that these molecules play different roles in the response of cardiomyocytes to LVH. (C) 1997 Academic Press Limited.