Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes
Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes
复制标题
DOI：
10.1093/cvr/cvv260
复制
发表时间：
2016-03-01
影响因子：
10.8
通讯作者：
Diez-Juan, Antonio
中科院分区：
文献类型：
--
作者：
Garcia, Nahuel A.;Moncayo-Arlandi, Javier;Diez-Juan, Antonio
心肌细胞（CM）和内皮细胞（EC）具有密切的解剖关系，这对于维持心脏的代谢需求至关重要。很少有人知道的机制，调节营养流从内皮细胞相关的CM，特别是在急性应激的情况下，当需要局部主动过程来调节内皮细胞的运输。我们研究了CM来源的exosomes是否可以调节EC的葡萄糖转运和代谢，在葡萄糖剥夺条件下，CM增加exosomes的合成和分泌。这些外泌体装载有功能性葡萄糖转运蛋白和糖酵解酶，这些酶被EC内化，导致受体细胞中葡萄糖摄取、糖酵解活性和丙酮酸产生增加。将允许EC快速响应以增加葡萄糖转运和从血液到CM的代谢燃料的推定摄取。这种CM-EC蛋白互补过程可能对健康和疾病的代谢调节有影响。
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.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.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.