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BMC Cell Biol. 2016 Jun 23;17(1):25. doi: 10.1186/s12860-016-0100-1.

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

Author information

1
Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
2
Section of Endocrinology, Department of Medicine, Temple University School of Medicine, 3500 North Broad Street, Room 480A, Philadelphia, PA, 19140, USA.
3
Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
4
Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China. song_junqiu@126.com.
5
Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China. liu_yanxia126@126.com.

Abstract

BACKGROUND:

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. 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.

RESULTS:

H/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.

CONCLUSION:

We 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.

KEYWORDS:

Apoptosis; Endothelial microvesicles; H9c2 cardiomyocytes; Hypoxia/reoxygenation; Oxidative stress

PMID:
27338159
PMCID:
PMC4919832
DOI:
10.1186/s12860-016-0100-1
[Indexed for MEDLINE]
Free PMC Article

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