Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells

PLoS One. 2015 Sep 22;10(9):e0138849. doi: 10.1371/journal.pone.0138849. eCollection 2015.

Abstract

Cardiomyocytes (CMs) and endothelial cells (ECs) have an intimate anatomical relationship that is essential for maintaining normal development and function in the heart. Little is known about the mechanisms that regulate cardiac and endothelial crosstalk, particularly in situations of acute stress when local active processes are required to regulate endothelial function. We examined whether CM-derived exosomes could modulate endothelial function. Under conditions of glucose deprivation, immortalized H9C2 cardiomyocytes increase their secretion of exosomes. CM-derived exosomes are loaded with a broad repertoire of miRNA and proteins in a glucose availability-dependent manner. Gene Ontology (GO) analysis of exosome cargo molecules identified an enrichment of biological process that could alter EC activity. We observed that addition of CM-derived exosomes to ECs induced changes in transcriptional activity of pro-angiogenic genes. Finally, we demonstrated that incubation of H9C2-derived exosomes with ECs induced proliferation and angiogenesis in the latter. Thus, exosome-mediated communication between CM and EC establishes a functional relationship that could have potential implications for the induction of local neovascularization during acute situations such as cardiac injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiology
  • Exosomes / metabolism*
  • Glucose / administration & dosage*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism
  • Myocytes, Cardiac / metabolism*
  • Neovascularization, Physiologic*
  • Rats
  • Rats, Wistar
  • Transcription, Genetic

Substances

  • MicroRNAs
  • Glucose

Grant support

N.A.G. acknowledges a fellowship from Erasmus Mundus Eurotango Program. I.O-O acknowledges Instituto de Investigación Sanitaria La Fe for a postdoctoral fellowship. A.D.J. acknowledges support from Ramon y Cajal Program (RYC-2008-02378). P.S. acknowledges support from PI10/743, PI13/414 grants, RETICS and Miguel Servet I3SNS Program (ISCIII). IGENOMIX provided support in the form of salaries for authors A D-J, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section