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PLoS One. 2014 Jan 2;9(1):e85396. doi: 10.1371/journal.pone.0085396. eCollection 2014.

EPC-derived microvesicles protect cardiomyocytes from Ang II-induced hypertrophy and apoptosis.

Author information

1
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.
2
Department of Cardiology, the People's Hospital of Sanya, Sanya, China.
3
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.
4
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.
5
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Ohio, United States of America.
6
Department of Neurology, the Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China.

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.

PMID:
24392165
PMCID:
PMC3879348
DOI:
10.1371/journal.pone.0085396
[Indexed for MEDLINE]
Free PMC Article

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