Reduced Histone Deacetylase 3 Attenuates Cardiac Microvascular Endothelial Cell Injury after Myocardial Ischemia-Reperfusion Injury by Elevating microRNA-17-3p and Inhibiting Cylindromatosis

Abstract

Objective: Recently, the role of microRNAs (miRNAs) in human disease has been widely studied, this research aims to assess the effects of miR-17-3p and histone deacetylase 3 (HDAC3) on myocardial ischemia-reperfusion injury (MIRI). Methods: The I/R rat models were established by left coronary artery ligation, which were conducted with silenced HDAC3 plasmid, miR-17-3p mimics or inhibitors, and then the expression of miR-17-3p, HDAC3 and cylindromatosis, pathological changes, cardiac function, apoptosis of cardiac microvascular endothelial cells (CMECs), vascular endothelial injury and oxidative stress were measured. In cellular experiment, the cultured CMECs were conducted with hypoxia-reoxygenation (H/R) to establish cell models, which were also treated with silenced HDAC3 plasmid, miR-17-3p mimics or inhibitors, then the expression of miR-17-3p, HDAC3 and cylindromatosis, cell viability, angiogenesis ability, migration and apoptosis of CMECs were assessed. Results: MiR-17-3p was downregulated, while HDAC3 and cylindromatosis were upregulated in I/R rats and H/R CMECs. The inhibited HDAC3 and elevated miR-17-3p could promote cardiac function but ameliorate infarct size, vascular endothelial injury and oxidative stress, while restrict apoptosis of CMECs of I/R rats, and also promote cell viability, angiogenesis ability and migration, while decelerate apoptosis of H/R CMECs. Conclusion: We have found that the reduced HDAC3 could attenuate CMEC injury in MIRI by elevating miR-17-3p and inhibiting cylindromatosis, which may contribute to MIRI treatment. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81760780 and 81860769), The Outstanding Youth Project of Inner Mongolia Natural Science Foundation (No. 2018JQ01), The Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (No.NJYT-17-A06 and NJYT-19-B14) Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement:Animal experiments were strictly in accordance with the Guide to the Management and Use of Laboratory Animals issued by the National Institutes of Health. The protocol of animal experiments was approved by the Institutional Animal Care and Use Committee of Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for The Nationalities.