EndophilinA2 protects against angiotensin II-induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes
EndophilinA2 protects against angiotensin II-induced cardiac hypertrophy by inhibiting angiotensin II type 1 receptor trafficking in neonatal rat cardiomyocytes
复制标题
EndophilinA2 通过抑制新生大鼠心肌细胞中血管紧张素 II 1 型受体的运输来防止血管紧张素 II 诱导的心脏肥大
DOI：
10.1002/jcb.26862
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发表时间：
2018-11-01
影响因子：
4
通讯作者：
Luo, Jian-Dong
中科院分区：
文献类型：
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作者：
Liu, Yun;Shen, Huan-Jia;Luo, Jian-Dong
心肌肥厚是慢性心力衰竭的主要危险因素之一。内嗜蛋白A2（EndoA 2）在网格蛋白介导的内吞作用和网格蛋白非依赖性内吞作用中的作用已被充分证明。在本研究中，我们测试了这一假设，即EndoA 2保护血管紧张素II（Ang II）诱导的心肌肥大，通过介导细胞内血管紧张素II 1型受体（AT 1-R）运输的新生大鼠心肌细胞（NRCMs）。通过使用细胞表面积和定量RT-PCR（qPCR）分析评价心肌肥大。我们首次发现，EndoA 2减弱了由Ang II诱导的心脏肥大和纤维化。此外，EndoA 2抑制过度内质网应激（ERS）诱导的细胞凋亡，这解释了EndoA 2对心肌肥厚的有益作用。我们进一步揭示了EndoA 2和AT 1-R之间存在相互作用。Ang Ⅱ处理后，抑制AT 1-R由胞浆向胞膜转运的EndoA 2的表达水平明显降低，EndoA 2与AT 1-R的相互作用也明显减弱。此外，Ang II抑制AT 1-R与GRP-78的共定位，这被EndoA 2过表达逆转。结论：EndoA 2可能通过抑制AT 1-R从细胞质向细胞膜的转运而抑制信号转导，从而对Ang Ⅱ诱导的心肌肥厚起保护作用。
Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin-mediated endocytosis and clathrin-independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)-induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1-R) trafficking in neonatal rat cardiomyocytes (NRCMs). Cardiac hypertrophy was evaluated by using cell surface area and quantitative RT-PCR (qPCR) analyses. For the first time, we found that EndoA2 attenuated cardiac hypertrophy and fibrosis induced by Ang II. Moreover, EndoA2 inhibited apoptosis induced by excessive endoplasmic reticulum stress (ERS), which accounted for the beneficial effects of EndoA2 on cardiac hypertrophy. We further revealed that there was an interaction between EndoA2 and AT1-R. The expression levels of EndoA2, which inhibits AT1-R transport from the cytoplasm to the membrane, and the interaction between EndoA2 and AT1-R were obviously decreased after Ang II treatment. Furthermore, Ang II inhibited the co-localization of AT1-R with GRP-78, which was reversed by EndoA2 overexpression. In conclusion, our results suggested that EndoA2 plays a role in protecting against cardiac hypertrophy induced by Ang II, possibly by inhibiting AT1-R transport from the cytoplasm to the membrane to suppress signal transduction.