Wenzel S, Schorr K, Degenhardt H, Frischkopf K, Kojda G, Wiesner R J, Rosenkranz S, Piper H M, Schlüter K D
Physiologisches Institut, Justus-Liebig-Universität Giessen, Germany.
J Mol Cell Cardiol. 2001 Jun;33(6):1181-90. doi: 10.1006/jmcc.2001.1382.
Parathyroid hormone-related peptide (PTHrP) is expressed throughout the cardiovascular system including coronary endothelial cells. Factors involved in 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 isolated from ventricles of adult rats and PTHrP protein expression in these cultures was analysed by immunoblotting. TGF-beta(1)caused a concentration-dependent reduction in PTHrP protein within 24 h. In transgenic mice over-expressing TGF-beta(1)ventricular PTHrP protein expression and release was reduced compared to non-transgenic littermates. Similar concerns hold for PTHrP mRNA content (RT-PCR). Since ventricular TGF-beta(1)expression increases under pathophysiological conditions like arterial hypertension, ventricular PTHrP expression was further determined in aging spontaneously hypertensive (SHR-SP) and normotensive rats. TGF- beta(1)expression was increased 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 which 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 expression was reduced under all conditions in which coronary endothelial cells were exposed to TGF-beta(1). PTHrP expression does not correlate with cardiac hypertrophy. Since coronary endothelial cells represent the majority of PTHrP producing cells in the ventricle its downregulation by TGF- beta(1)seems to be relevant for the paracrine effects of PTHrP.
甲状旁腺激素相关肽（PTHrP）在包括冠状动脉内皮细胞在内的整个心血管系统中均有表达。此前尚未对参与心脏PTHrP表达调控的因素进行过研究。本研究调查了转化生长因子（TGF）-β1对心室PTHrP表达的影响。从成年大鼠心室中分离出冠状动脉内皮细胞，并通过免疫印迹分析这些培养物中PTHrP蛋白的表达。TGF-β1在24小时内导致PTHrP蛋白呈浓度依赖性降低。在过表达TGF-β1的转基因小鼠中，与非转基因同窝小鼠相比，心室PTHrP蛋白表达和释放减少。PTHrP mRNA含量（逆转录聚合酶链反应）也有类似情况。由于在动脉高血压等病理生理条件下心室TGF-β1表达会增加，因此进一步测定了衰老自发性高血压（SHR-SP）大鼠和正常血压大鼠的心室PTHrP表达。10月龄时，SHR-SP大鼠的TGF-β1表达增加，心室PTHrP mRNA表达下调。在TGF-β1表达再次恢复正常的老年SHR-SP大鼠中，PTHrP表达未恢复。最后，我们研究了升主动脉结扎后大鼠的心室PTHrP表达，升主动脉结扎会产生压力诱导的心肌肥大，但不会诱导TGF-β1表达。在这些动物的心室中，PTHrP表达在第3天短暂增加并恢复正常。总之，在冠状动脉内皮细胞暴露于TGF-β1的所有条件下，PTHrP表达均降低。PTHrP表达与心肌肥大无关。由于冠状动脉内皮细胞是心室中产生PTHrP的主要细胞，TGF-β1对其下调似乎与PTHrP的旁分泌作用相关。
