Micro-RNA-93-5p and micro-RNA-3613-5p in exosomes released from vascular endothelial cells regulate medial arterial calcification in hemodialysis patients

Abstract

Abstract Objective: To determine the underlying mechanism for how circulating exosomes with micro-RNA (Exo-miRNA) cargos promote medial arterial calcification (MAC) in maintenance hemodialysis (MHD) patients. Methods and Results: Plasma samples and fistular vascular tissues were collected from 12 MHD patients. Histological examinations and Exo-miRNA aberrant expression assays were conducted on the samples. The Exo-miRNAs in supernatants of human umbilical vein endothelial cells (HUVECs) treated with asymmetric dimethylarginine (ADMA) were compared with those in control HUVECs. Two similar miRNAs between patient plasma samples and cell culture supernatants, miR-93-5p and miR-3613-5p, were selected for cell culture experiments in vitro. Human aortic smooth muscle cells (HASMCs) were incubated with mimics of these miRNAs or cocultured with ADMA-treated HUVECs using a transwell system. Target proteins in the cell lysates were detected by western blotting. The histological examinations provided images of MAC Compared with control HASMCs, up-regulation of S100A11a, PI3K p110α, NF-κB, p38 MAPK, Rab11a, and F-actin was observed in the miR-93-5p mimic group, while up-regulation of Rab11a and F-actin was noted in the miR-3613-5p mimic group. Conclusion: MiRNA-93-5p and miRNA-3613-5p in exosomes released from vascular endothelial cells enter into vascular smooth muscle cells and regulate MAC in MHD patients.