Protective effects of acetylcholine on hypoxia-induced endothelial-to-mesenchymal transition in human cardiac microvascular endothelial cells
- 1 October 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular and Cellular Biochemistry
- Vol. 473 (1-2), 101-110
- https://doi.org/10.1007/s11010-020-03811-w
Abstract
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-kappa B activation in HCMECs. ACh also reduced hypoxia-inducible factor (HIF)-1 & x251; protein levels under hypoxia. Knock down of HIF-1 & x251; enhanced the inhibitory effect of ACh on NF-kappa B activation. The NF-kappa B-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-kappa B and the induction of autophagy.Funding Information
- National Natural Science Foundation of China (81860052, 81871113)
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