title: EPC-derived microvesicles protect cardiomyocytes from Ang II-induced hypertrophy and apoptosis.
abstract: Cell-released microvesicles (MVs) represent a novel way of cell-to-cell communication. Previous evidence indicates that endothelial progenitor cells (EPCs)-derived MVs can modulate endothelial cell survival and proliferation. In this study, we evaluated whether EPC-MVs protect cardiomyocytes (CMs) against angiotensin II (Ang II)-induced hypertrophy and apoptosis. The H9c2 CMs were exposed to Ang II in the presence or absence of EPC-MVs. Cell viability, apoptosis, surface area and β-myosin heavy chain (β-MHC) expression were analyzed. Meanwhile, reactive oxygen species (ROS), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS), and their phosphorylated proteins (p-Akt, p-eNOS) were measured. Phosphatidylinositol-3-kinase (PI3K) and NOS inhibitors were used for pathway verification. The role of MV-carried RNAs in mediating these effects was also explored. Results showed 1) EPC-MVs were able to protect CMs against Ang II-induced changes in cell viability, apoptosis, surface area, β-MHC expression and ROS over-production; 2) The effects were accompanied with the up-regulation of Akt/p-Akt and its downstream eNOS/p-eNOS, and were abolished by PI3K inhibition or partially blocked by NOS inhibition; 3) Depletion of RNAs from EPC-MVs partially or totally eliminated the effects of EPC-MVs. Our data indicate that EPC-MVs protect CMs from hypertrophy and apoptosis through activating the PI3K/Akt/eNOS pathway via the RNAs carried by EPC-MVs.
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Ohio, United States of America ; Department of Gerontology, the Affiliated Hospital of Hainan Medical College, Haikou, China.
authors.forename: Shenhong
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Cardiology, the People's Hospital of Sanya, Sanya, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Ohio, United States of America ; Department of Neurology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Ohio, United States of America ; Department of Cardiology, the People's Hospital of Sanya, Sanya, China.
authors.forename: Ruilian
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Ohio, United States of America.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Neurology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Cardiology, the People's Hospital of Sanya, Sanya, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Ohio, United States of America ; Department of Neurology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D006984:Hypertrophy; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012313:RNA / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D012313:RNA; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt