High glucose promotes atherosclerosis by regulating miRNA let7d-5p level

BackgroundMiRNA let7d-5p has been recently reported to be abnormally expressed in diabetes-associated atherosclerosis (AS). However, it still remains unknown how let7d-5p contributes to the process of atherosclerosis.MethodsTwenty fresh tissues and a total of 28 wax block specimens from carotid endarterectomy procedures were obtained from the Luoyang Central Hospital affiliated to Zhengzhou University. The expression of let7d-5p was assessed using quantitative RT-PCR (qRT-PCR). A series of in vitro experiments was used to determine the roles of let7d-5p knockdown and overexpression in vascular smooth muscle cells (VSMCs).ResultsWe discovered that the carotid plaques from diabetic patients had lower expression levels of miR let7d-5p. In VSMCs, the expression of miRNA let7d-5p was significantly lower in high glucose conditions compared with low glucose situations. The proliferation and migration of VSMCs were also inhibited by the overexpression of let7d-5p, whereas the opposite was true when let7d-5p was inhibited, according to gain and loss of function studies. Mechanically, let7d-5p might activate the GSK3 beta/beta-catenin signaling pathway via binding to the high mobility group AT-Hook 2 (HMGA2) mRNA in VSMCs. Additionally, GLP-1RA liraglutide may prevent the migration and proliferation of VSMCs by raising let7d-5p levels.ConclusionsHigh glucose stimulated the proliferation and migration of VSMCs by regulating the let7d-5p/HMGA2/GSK3 beta/beta-catenin pathway, and liraglutide may slow atherosclerosis by increasing the levels of miR let7d-5p. In this study, we reported that the miR let7d-5p expression was decreased in the carotid plaque of patients with diabetes. We first revealed high glucose promoted the proliferation and migration of VSMCs by regulating the let7d-5p/HMGA2/GSK3 beta/beta-catenin pathway, and liraglutide may alleviate atherosclerosis via up-regulating miR let7d-5p levels. GLP-1RA liraglutide could inhibit the proliferation and migration of VSMCs by up-regulating the level of let7d-5p.dagger image