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Protective effects of acetylcholine on hypoxia-induced endothelial-to-mesenchymal transition in human cardiac microvascular endothelial cells.
Molecular and Cellular Biochemistry ( IF 4.3 ) Pub Date : 2020-06-29 , DOI: 10.1007/s11010-020-03811-w
Zhiyang Li 1 , Xuelian Li 2, 3 , Yeqian Zhu 4 , Qiushi Chen 4 , Bingong Li 2, 3 , Fengxiang Zhang 4, 5
Affiliation  

Endothelial-to-mesenchymal transition (EndMT) has been reported as a key factor in myocardial fibrosis. Acetylcholine (ACh), a neurotransmitter of the vagus nerve, has been confirmed to exert cardio-protective properties with unclear mechanisms. In this study, the specific markers of cell injury, EndMT, inflammation, and autophagy were measured. We found that treatment with ACh prevented hypoxia-induced cell viability reduction and apoptosis in human cardiac microvascular endothelial cells (HCMECs). Additionally, our results indicate that pre-treatment with ACh significantly suppresses hypoxia-induced EndMT and NF-κB activation in HCMECs. ACh also reduced hypoxia-inducible factor (HIF)-1ɑ protein levels under hypoxia. Knock down of HIF-1ɑ enhanced the inhibitory effect of ACh on NF-κB activation. The NF-κB-specific small molecule inhibitor BAY 11-7082, prostaglandin E2, and LY294002 prevented hypoxia-induced EndMT. Moreover, our data show that hypoxia triggers autophagy in HCMECs, and ACh significantly upregulates autophagy activity. Pre-treatment of HCMECs with 3-methyladenine or chloroquine partially reversed ACh-induced EndMT inhibition. These results suggest that ACh may confer protection against hypoxia-induced EndMT through the inhibition of NF-κB and the induction of autophagy.



中文翻译:

乙酰胆碱对缺氧诱导的人微血管内皮细胞内皮向间充质转化的保护作用。

内皮细胞向间质转化(EndMT)已被报道为心肌纤维化的关键因素。迷走神经的神经递质乙酰胆碱(ACh)已被证实具有心血管保护特性,但机制尚不清楚。在这项研究中,测量了细胞损伤,EndMT,炎症和自噬的特异性标记。我们发现用ACh进行的治疗可防止缺氧诱导的人心肌微血管内皮细胞(HCMEC)的细胞活力降低和凋亡。此外,我们的结果表明,用ACh预处理可显着抑制HCMECs中低氧诱导的EndMT和NF-κB活化。在低氧条件下,ACh还可以降低低氧诱导因子(HIF)-1ɑ蛋白水平。抑制HIF-1ɑ可增强ACh对NF-κB活化的抑制作用。NF-κB特异性小分子抑制剂BAY 11-7082,前列腺素E2和LY294002可防止缺氧诱导的EndMT。此外,我们的数据表明,缺氧会触发HCMEC中的自噬,而ACh会显着上调自噬活性。用3-甲基腺嘌呤或氯喹对HCMEC进行预处理可以部分逆转ACh诱导的EndMT抑制。这些结果表明,ACh可通过抑制NF-κB和诱导自噬而赋予针对缺氧诱导的EndMT的保护作用。

更新日期:2020-06-30
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