TGF-beta(1) downregulates PTHrP in coronary endothelial cells

Parathyroid hormone-related peptide (PTHrP) is expressed throughout the car diovascular system including coronary endothelial cells. Factors involved i n the regulation of cardiac PTHrP expression have not been examined before. This study investigates the influence of transforming growth factor (TGF)- beta (1) on ventricular PTHrP expression. Coronary endothelial cells were i solated from ventricles of adult rats and PTHrP protein expression in these cultures was analysed by immunoblotting. TGF-beta (1) caused a concentrati on-dependent reduction in PTHrP protein within 24 h. In transgenic mice ove r-expressing TGF-beta (1) ventricular PTHrP protein expression and release was reduced compared to non-transgenic littermates. Similar concerns hold f or PTHrP mRNA content (RT-PCR). Since ventricular TGF-beta (1) expression i ncreases under pathophysiological conditions like arterial hypertension, ve ntricular PTHrP expression was further determined in aging spontaneously hy pertensive (SHR-SP) and normotensive rats. TGF-beta (1) expression was incr eased in SHR-SP and ventricular PTHrP mRNA expression was downregulated at the age of 10 months. PTHrP expression did not recover in elder SHR-SP in w hich TGF-beta (1) expression was normalized again. Finally, we investigated ventricular PTHrP expression in rats after banding of the ascending aorta which generates a pressure induced hypertrophy without an induction of TGF- beta (1) expression. In ventricles from these animals, PTHrP expression was transiently increased and normalized at day 3. In conclusion, PTHrP expres sion was reduced under all conditions in which coronary endothelial cells w ere exposed to TGF-beta (1). PTHrP expression does not correlate with cardi ac hypertrophy. Since coronary endothelial cells represent the majority of PTHrP producing cells in the ventricle its downregulation by TGF-beta (1) s eems to be relevant for the paracrine effects of PTHrP. (C) 2001 Academic P ress.