title: Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes.
abstract: OBJECTIVE
  Cardiomyocytes (CMs) and endothelial cells (ECs) have an intimate anatomical relationship, which is essential for maintaining the metabolic requirements of the heart. Little is known about the mechanisms that regulate nutrient flow from ECs to associated CMs, especially in situations of acute stress when local active processes are required to regulate endothelial transport. We examined whether CM-derived exosomes can modulate glucose transport and metabolism in ECs.
  
  
  RESULTS
  In conditions of glucose deprivation, CMs increase the synthesis and secretion of exosomes. These exosomes are loaded with functional glucose transporters and glycolytic enzymes, which are internalized by ECs, leading to increased glucose uptake, glycolytic activity, and pyruvate production in recipient cells.
  
  
  CONCLUSIONS
  These findings establish CM-derived exosomes as key components of the cardio-endothelial communication system which, through intercellular protein complementation, would allow a rapid response from ECs to increase glucose transport and a putative uptake of metabolic fuels from blood to CMs. This CM-EC protein complementation process might have implications for metabolic regulation in health and disease.
authors.affiliation: Mixt 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: Cardiovascular Genetics Center, Institut d́Investigació Biomèdica de Girona, Girona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moncayo-Arlandi
authors.affiliation: Mixt Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Adva. Fernando Abril Martorell 106, 46026 Valencia, Spain pilar.sepulveda.sanchis@gmail.com antonio.diez@igenomix.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Sepulveda
authors.affiliation: Fundación IVI/INCLIVA, Valencia, Spain IGENOMICS, Calle Catedrático Agustín Escardino 9, Paterna, Valencia 46980, Spain pilar.sepulveda.sanchis@gmail.com antonio.diez@igenomix.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Diez-Juan
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D005947:Glucose
keywords: Cardiomyocyte; Endothelium; Exosomes; Glycolysis; Protein complementation