Extracellular vesicle microRNA cargoes from intermittent hypoxia-exposed cardiomyocytes and their effect on endothelium

Yu Li,Huina Zhang,Yunhui Du,Lu Peng,Yanwen Qin,Huirong Liu,Xinliang Ma,Yongxiang Wei

doi:10.1016/j.bbrc.2021.02.034

Abstract

Intermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, is an independent risk factor of cardiovascular complications. However, the mechanism has not been fully elucidated. Growing evidence has revealed alterations of extracellular vesicle (EV) contents, mostly miRNAs, playing a pathogenic role in cardiovascular complications. In current study, we attempt to compare the disparity of myocardial EV miRNA components after IH or normoxia treatment and determine whether EVs from IH-treated cardiomyocytes could affect endothelial function. 63 differentially expressed miRNAs were identified in EVs from IH-exposed cardiomyocytes by miRNA chip assay. Among them, 16 miRNAs with homologous sequence in mouse and human were verified by qPCR assay and 11 miRNAs were proved with the same tendency as miRNA chip assay. KEGG predicted that the function of differentially expressed miRNA was enriched to Akt signaling pathway. Notably, EVs from IH-exposed cardiomyocytes dramatically impaired endothelial-dependent relaxation and inhibited Akt/eNOS expression in endothelial cells. This study provides the first evidence that IH significantly alters myocardial EV miRNA composition and reveals a novel role of myocardial EVs in endothelial function under IH status, which will help to understand the OSA- or IH-related endothelial dysfunction from a new scope.

Highlights

Intermittent hypoxia (IH), as the crucial pathophysiological feature of obstructive sleep apnea syndrome (OSAS), is an independent risk factor initiating the progression of cardiovascular complications
This study provides the first evidence that IH causes significant alteration in myocardial Extracellular vesicle (EV) miRNA composition, which may contribute to IH or OSAS-triggered cardiovascular injury and organ-to-organ communication
Obstructive sleep apnea syndrome (OSAS) is an independent risk factor associated with many clinical complications [1]

Summary

Introduction

Intermittent hypoxia (IH), as the crucial pathophysiological feature of obstructive sleep apnea syndrome (OSAS), is an independent risk factor initiating the progression of cardiovascular complications. How IH cause cardiovascular injury and initiate inter-organ communication remains unclear. Extracellular vesicle (EV) are reported to be involved in cell-to-cell and organ-to-organ communications through selectively carrying RNA and protein cargos from donor cells and delivering them to recipient cells. By utilizing an unbiased miRNA microarray approach, current study attempted to determine whether IH may alter miRNA profiles in cardiomyocyte-derived extracellular vesicles and whether EVs from IH-treated cardiomyocytes could affect endothelial function

Results

Discussion

Conclusion