title: Microvesicles derived from hypoxia/reoxygenation-treated human umbilical vein endothelial cells promote apoptosis and oxidative stress in H9c2 cardiomyocytes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Shang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin, 300070, People's Republic of China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Section of Endocrinology, Department of Medicine, Temple University School of Medicine, 3500 North Broad Street, Room 480A, Philadelphia, PA, 19140, USA.|Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Minglin
authors.initials: M
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Junqiu
authors.initials: J
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010100:Oxygen
keywords: Apoptosis; Endothelial microvesicles; H9c2 cardiomyocytes; Hypoxia/reoxygenation; Oxidative stress