TGF-beta(1) and prepro-ANP mRNAs are differentially regulated in exercise-induced cardiac hypertrophy

The induction of transforming growth factor (TGF)-beta and prepro- atrial n atriuretic peptide (ANP) mRNAs represent hallmark features of pathological cardiac hypertrophy. The present study examined whether this pattern of mRN A expression was conserved in a physiological model of cardiac hypertrophy. To address this thesis, female Sprague-Dawley rats were individually house d and permitted to run freely. Voluntary exercise for 3 and 6 wk resulted i n biventricular hypertrophy and increased cytochrome c oxidase activity in the triceps muscle. In the hypertrophied left ventricle, the steady-state m RNA level of the cardiac fetal gene prepro- ANP and the extracellular matri x proteins preprocollagen-alpha (1) and fibronectin were similar in exercis e-trained and sedentary rats. By contrast, an increased expression of TGF-b eta (1) mRNA was observed, whereas TGF-beta (3) mRNA level was unchanged in the hypertrophied left ventricle of exercise-trained compared with sedenta ry rats. These data highlight a heterogeneity in the regulation of TGF-beta isoforms, and the increased expression of ventricular TGF-beta (1) mRNA in physiological cardiac hypertrophy may contribute to myocardial remodeling.