Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

Abstract

The aim of the present study was to investigate the function and mechanism of action of microRNA (miRNA or miR)-199a-3p in vascular endothelial cell injury induced by type 2 diabetes mellitus (T2DM). A total of 36 patients with T2DM (26 males and 10 females; mean age, 52.5±7.0 years) and 20 healthy subjects (10 males and 10 females; mean age, 55.6±4.5 years) were included in the present study. Peripheral blood samples were obtained from all participants and total RNA was extracted Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-199a-3p. Following the transfection of human umbilical vein endothelial cells (HUVECs) with a negative control (NC) miRNA or miR-199a-3p mimics, cell proliferation was assessed using a Cell Counting kit-8 assay. Cell migration was investigated using Transwell assays and flow cytometry was performed to detect the apoptosis of HUVECs. HUVECs were infected with Ad-GFP-LC3B and laser-scanning confocal microscopy was performed to observe autophagosomes in HUVECs. Western blotting was used to measure the expression of proteins associated with autophagy and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB signaling pathway. MiR-199a-3p was downregulated in peripheral blood from patients with T2DM compared with healthy subjects. Transfection with miR-199a-3p mimics promoted the proliferation and migration of HUVECs. However, miR-199a-3p overexpression inhibited the apoptosis of HUVECs. MiR-199a-3p facilitated HUVEC autophagy by affecting autophagy-associated signaling pathways. Furthermore, miR-199a-3p regulated the biological functions of HUVECs via the PI3K/AKT/NF-κB signaling pathway. The results of the present study suggest that miR-199a-3p expression was reduced in patients with T2DM compared with healthy subjects and may be associated with vascular endothelial cell injury. In addition, miR-199a-3p promoted the proliferation, migration and autophagy of HUVECs, potentially by regulating the PI3K/AKT/NF-κB signaling pathway. Therefore, miR-199a-3p may function as protector of vascular endothelia.

Dexmedetomidine protects PC12 cells from oxidative damage through regulation of miR-199a/HIF-1α

“…In addition to this, it was affirmed that the abnormal miR-199a expression was together with the generation of ROS [35,36]. Along with the deepened study gradually, a mass of researches released that miR-199a repressed cell viability and accelerated apoptosis [37]. The above results of all researches were similar to our data.…”

MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema

“…The only miRNA whose previously reported role is in line with that reported herein is miR-199a-3p. Although implicated in a variety of carcinomas as either a repressor or promoter, miR-199a-3p has been found to be downregulated in the animal model of DR, thus confirming the protective role in both the AH and plasma reported here [ 7 , 33 ].…”

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

“…Diabetes Mellitus (DM) is a heterogeneous disorder characterized by a loss in glucose homeostasis and insulin resistance [131]. DM is a CV risk factor, and hyperglycemia is associated with chronic endothelium inflammation and endothelial dysfunction [132][133][134][135][136][137].…”

“…Other compounds with the same features, such as osthol [144] and phosphocreatinin [145] have been studied, and have shown similar effects and benefits. Moreover, high-density lipoproteins (HDL) [136] and microRNA-199a-3p [137] promote EC proliferation and migration under hyperglycemic conditions, activating different signaling pathways and promoting repair of the damaged vascular endothelium. These findings suggest that HDL and microRNA-199a-3p may be considered as potential therapeutic targets [136,137].…”