Nahuel A Garcia1, Javier Moncayo-Arlandi2, Pilar Sepulveda3, Antonio Diez-Juan4. 1. Mixt Unit for Cardiovascular Repair, Instituto de Investigación Sanitaria La Fe-Centro de Investigación Príncipe Felipe, Valencia, Spain. 2. Cardiovascular Genetics Center, Institut d́Investigació Biomèdica de Girona, Girona, Spain. 3. 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. 4. Fundación IVI/INCLIVA, Valencia, Spain IGENOMICS, Calle Catedrático Agustín Escardino 9, Paterna, Valencia 46980, Spain pilar.sepulveda.sanchis@gmail.com antonio.diez@igenomix.com.
Abstract
AIMS: 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. METHODS AND 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. CONCLUSION: 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. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: 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. METHODS AND 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. CONCLUSION: 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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Guy Eelen; Pauline de Zeeuw; Lucas Treps; Ulrike Harjes; Brian W Wong; Peter Carmeliet Journal: Physiol Rev Date: 2018-01-01 Impact factor: 37.312