Involvement of calcium-sensing receptor in cardiac hypertrophy-induced by angiotensinII through calcineurin pathway in cultured neonatal rat cardiomyocytes
Involvement of calcium-sensing receptor in cardiac hypertrophy-induced by angiotensinII through calcineurin pathway in cultured neonatal rat cardiomyocytes
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钙敏感受体通过钙调磷酸酶途径参与血管紧张素II诱导的培养新生大鼠心肌细胞心肌肥大
DOI：
10.1016/j.bbrc.2008.02.053
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发表时间：
2008-05-02
影响因子：
3.1
通讯作者：
Xu, Chang-qing
中科院分区：
文献类型：
--
作者：
Wang, Li-na;Wang, Chao;Xu, Chang-qing
心肌肥厚是心血管疾病常见的病理改变。近年来有研究表明，钙敏感受体（CaSR）在心血管组织中有表达。然而，CaSR在心肌肥厚中的功能参与仍不清楚。以往的研究表明，CaSR引起磷酸肌醇的积累，增加细胞内钙的释放。此外，钙依赖性磷酸酶钙调神经磷酸酶（CaN）在心肌肥厚的发展中起着至关重要的作用。因此，我们研究了CaSR在血管紧张素II（AngII）诱导的心肌肥厚中的表达以及GdCl 3激活CaSR对相关信号转导通路的影响。结果表明，AngII可诱导心肌肥厚，上调CaSR表达，增加心肌细胞内钙离子浓度（[Ca2+]（i）），激活CaN肥大信号通路。与单独AngII相比，加入GdCl3后上述变化更明显。CaN特异性抑制剂CsA可明显抑制GdCl_3对心肌肥厚的影响。这些结果表明，在培养的新生大鼠心肌细胞中，CaSR通过CaN通路参与AngII诱导的心肌肥厚。(C)2008年爱思唯尔公司All rights reserved.
Cardiac hypertrophy is a common pathological change accompanying cardiovascular disease. Recently, some evidence indicated that calcium-sensing receptor (CaSR) expressed in the cardiovascular tissue. However, the functional involvement of CaSR in cardiac hypertrophy remains unclear. Previous studies have shown that CaSR caused accumulation of inositol phosphate to increase the release of intracellular calcium. Moreover, Ca2+-dependent phosphatase calcineurin (CaN) played a vital role in the development of cardiac hypertrophy. Therefore, we investigated the expression of CaSR in cardiac hypertrophy-induced by angiotensin II (AngII) and the effects of CaSR activated by GdCl3 on the related signaling transduction pathways. The results showed that AngII induced cardiac hypertrophy and up-regulated the expression of CaSR, meanwhile increased the intracellular calcium concentration ([Ca2+](i)) and activated CaN hypertrophic signaling pathway. Compared with AngII alone, the above changes were further obvious when adding GdCl3. But the effects of GdCl3 on the cardiac hypertrophy were attenuated by CsA, a specific inhibitor of CaN. In conclusion, these results suggest that CaSR is involved in cardiac hypertrophy-induced by AngII through CaN pathway in cultured neonatal rat cardiomyocytes. (C) 2008 Elsevier Inc. All rights reserved.