title: Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells.
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.
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe- Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Nahuel A
authors.initials: NA
authors.lastname: Garcia
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe- Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Imelda
authors.initials: I
authors.lastname: Ontoria-Oviedo
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe- Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Hernán
authors.initials: H
authors.lastname: González-King
authors.affiliation: Fundación IVI/INCLIVA, Valencia, Spain; IGENOMIX, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Diez-Juan
authors.affiliation: Mixed Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe- Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepúlveda
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D055354:Exosomes / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; D005947:Glucose