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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Cell-Derived Microparticles / chemistry
  • Cell-Derived Microparticles / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelial Cells / metabolism*
  • Hypertrophy
  • Mice
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Nitric Oxide Synthase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA / chemistry
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Stem Cells / metabolism*


  • Reactive Oxygen Species
  • Angiotensin II
  • RNA
  • Nitric Oxide Synthase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt