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首页> 外文期刊>Journal of Cellular Physiology >MicroRNA-214 Is Upregulated in Heart Failure Patients and Suppresses XBP1-Mediated Endothelial Cells Angiogenesis
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MicroRNA-214 Is Upregulated in Heart Failure Patients and Suppresses XBP1-Mediated Endothelial Cells Angiogenesis

机译:微rna - 214是调节心脏衰竭病人和抑制XBP1-Mediated内皮细胞的血管生成

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More and more miRNAs have been shown to regulate gene expression in the heart and dysregulation of their expression has been linked to cardiovascular diseases including the miR-199a/214 cluster. However, the signature of circulating miR-214 expression and its possible roles during the development of heart failure has been less well studied. In this study, we elucidated the biological and clinical significance of miR-214 dysregulation in heart failure. Firstly, circulating miR-214 was measured by quantitative PCR, and we found that miR-214 was upregulated in the serum of chronic heart failure patients, as well as in hypertrophic and failing hearts of humans and mice. Adeno-associated virus serotype 9 (AAV9)-mediated miR-214 silencing attenuates isoproterenol (ISO) infusion-induced cardiac dysfunction and impairment of cardiac angiogenesis in mice. Mechanistically, miR-214 overexpression reduces angiogenesis of HUVECs by targeting XBP1, an important transcription factor of unfolded protein response, and XBP1 silencing decreases HUVECs proliferation and angiogenesis similar to miR-214 overexpression. Furthermore, ectopic expression of XBP1 enhances endothelial cells proliferation and tube formation, and reverses anti-angiogenic effect of miR-214 over expression. All these findings suggest that miR-214 is an important regulator of angiogenesis in heart in vitro and in vivo, likely via regulating the expression of XBP1, and demonstrate that miR-214 plays an essential role in the control/inhibition of cardiac angiogenesis. J. Cell. Physiol. 230: 1964-1973, 2015. (c) 2015 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.
机译:越来越多的microrna调节基因表达的心脏和失调他们的表达有关心血管疾病包括mir - 199 a / 214集群。循环mir - 214表达及其可能的角色在心力衰竭的发展太好了。阐明生物和临床心里的重要性mir - 214失调失败。以定量PCR,我们发现mir - 214是慢性的调节血清中心力衰竭病人,以及肥厚性和人类和失败的心老鼠。(AAV9)介导mir - 214沉默变弱异丙肾上腺素(ISO) infusion-induced心脏功能障碍和心脏的损害血管生成在老鼠身上。超表达减少HUVECs的血管生成针对XBP1的一个重要的转录因子展开的蛋白质反应,XBP1沉默减少HUVECs增殖和血管生成类似于mir - 214超表达。XBP1的异位表达增强内皮细胞增殖和管形成逆转mir - 214的抗血管生成的影响表达式。mir - 214是一种血管生成的重要调节器在心脏在体外和体内,可能通过调节XBP1的表达证明mir - 214中扮演着重要的角色在控制/抑制心脏血管生成。2015. 生理学Wiley出版的期刊,Inc。

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