Microvesicles derived from hypoxia/reoxygenation-treated human umbilical vein endothelial cells promote apoptosis and oxidative stress in H9c2 cardiomyocytes.

Qi Zhang,Junqiu Song,Man Shang,Yao Wang,Yanxia Liu,Mengxiao Zhang,Yan Chen,Yanna Wu,Minglin Liu

doi:10.1186/s12860-016-0100-1

Abstract

BackgroundVascular endothelial dysfunction is the closely related determinant of ischemic heart disease (IHD). Endothelial dysfunction and ischemia/reperfusion injury (IRI) have been associated with an increase in microvesicles (MVs) in vivo. However, the potential contribution of endothelial microvesicles (EMVs) to myocardial damage is unclear. Here we aimed to investigate the role of EMVs derived from hypoxia/reoxygenation (H/R) -treated human umbilical vein endothelial cells (HUVECs) on cultured H9c2 cardiomyocytes.ResultsH/R injury model was established to induce HUVECs to release H/R-EMVs. The H/R-EMVs from HUVECs were isolated from the conditioned culture medium and characterized. H9c2 cardiomyocytes were then incubated with 10, 30, 60 μg/mL H/R-EMVs for 6 h. We found that H9c2 cells treated by H/R-EMVs exhibited reduced cell viability, increased cell apoptosis and reactive oxygen species (ROS) production. Moreover mechanism studies demonstrated that H/R-EMVs could induce the phosphorylation of p38 and JNK1/2 in H9c2 cells in a dose-dependent manner. In addition, H/R-EMVs contained significantly higher level of ROS than EMVs generated from untreated HUVECs, which might be a direct source to trigger a cascade of myocardial damage.ConclusionWe showed that EMVs released during H/R injury are pro-apoptotic, pro-oxidative and directly pathogenic to cardiomyocytes in vitro. EMVs carry ROS and they may impair myocardium by promoting apoptosis and oxidative stress. These findings provide new insights into the pathogenesis of IRI.

Highlights

Vascular endothelial dysfunction is the closely related determinant of ischemic heart disease (IHD)
Most of H/R-endothelial microvesicles (EMVs) externalized their endothelial cell marker CD144 (Fig. 1c). These results indicated that H/REMVs had a size of
In this study, we first established that EMVs could be generated from H/R-treated HUVECs

Summary

Introduction

Vascular endothelial dysfunction is the closely related determinant of ischemic heart disease (IHD). Endothelial dysfunction and ischemia/reperfusion injury (IRI) have been associated with an increase in microvesicles (MVs) in vivo. The pathological processes leading to IHD (including myocardial infarction, angina pectoris, or both) are very complicated and closely accompanied with ischemia/reperfusion injury (IRI) [1]. Increased levels of circulating MVs have been suggested in acute coronary ischemia, myocardial infarction and other IHD, and MVs are likely contributing to endothelial dysfunction, leukocyte adhesion, platelet activation and obstruction of blood flow [10]

Objectives

Methods

Results

Discussion

Conclusion