Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells.
Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells.
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DOI：
10.1371/journal.pone.0138849
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sepúlveda P
中科院分区：
文献类型：
--
作者：
Garcia NA;Ontoria-Oviedo I;González-King H;Diez-Juan A;Sepúlveda P
心肌细胞（CM）和内皮细胞（EC）具有密切的解剖关系，这对于维持心脏的正常发育和功能至关重要。关于调节心脏和内皮串扰的机制知之甚少，特别是在急性应激的情况下，需要局部活性过程来调节内皮功能。我们研究了CM衍生的外泌体是否可以调节内皮功能。在葡萄糖剥夺的条件下，永生化H9C2心肌细胞增加其外泌体的分泌。CM衍生的外泌体以葡萄糖可用性依赖性方式负载有广泛的miRNA和蛋白质库。外泌体货物分子的基因本体（GO）分析鉴定了可以改变EC活性的生物过程的富集。我们观察到，CM衍生的外泌体添加到EC诱导促血管生成基因的转录活性的变化。最后，我们证明了H9C2衍生的外泌体与EC的孵育诱导了后者的增殖和血管生成。因此，外泌体介导的CM和EC之间的通信建立了一个功能的关系，可能有潜在的影响，在急性情况下，如心脏损伤诱导局部新生血管形成。
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.