Yang Qinbo, Jia Chenglin, Wang Peiwei, Xiong Minqi, Cui Jingang, Li Li, Wang Wenjian, Wu Qingyu, Chen Yu, Zhang Teng
Yueyang Hospital and Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China; Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195, USA.
Int J Cardiol. 2014 Dec 20;177(3):925-34. doi: 10.1016/j.ijcard.2014.09.204. Epub 2014 Oct 8.
MicroRNAs are potent regulators of gene expression and may serve as disease markers. This study aimed to identify the plasma microRNA signature in hypertensive patients, which may help better understand the mechanisms underlying the pathogenesis of hypertension and target organ impairment.
Plasma samples from three independent cohorts were analyzed to identify circulating microRNA candidates associated with hypertension in patients. The results revealed that the plasma level of hsa-miR-505, a previously reported tumor suppressive microRNA, was significantly elevated in hypertensive patients. Further studies were carried out in endothelial cells to elucidate the functional significance of the enhanced level of hsa-miR-505. The results showed that hsa-miR-505 expression markedly impaired the migration and tube formation of all three types of endothelial cells examined. Moreover, gene expression analyses and luciferase reporter assay revealed that FGF18, a proangiogenic factor, is a target directly regulated by hsa-miR-505 in endothelial cells, which may in part underlie the function of hsa-miR-505 in angiogenic processes.
Our findings indicate that hsa-miR-505 is a novel circulating signature of hypertension, which may play a role in angiogenesis. Our results provide mechanistic insights into hypertension-associated pathogenesis and point hsa-miR-505 as a potential target for intervention of hypertension.
微小RNA是基因表达的有效调节因子，可能作为疾病标志物。本研究旨在识别高血压患者血浆中的微小RNA特征，这可能有助于更好地理解高血压发病机制及靶器官损害的潜在机制。
对来自三个独立队列的血浆样本进行分析，以识别与高血压患者相关的循环微小RNA候选物。结果显示，先前报道的具有肿瘤抑制作用的微小RNA hsa-miR-505在高血压患者血浆中的水平显著升高。在内皮细胞中进行了进一步研究，以阐明hsa-miR-505水平升高的功能意义。结果表明，hsa-miR-505的表达显著损害了所检测的三种内皮细胞的迁移和管腔形成。此外，基因表达分析和荧光素酶报告基因检测显示，促血管生成因子FGF18是内皮细胞中受hsa-miR-505直接调控的靶标，这可能部分解释了hsa-miR-505在血管生成过程中的作用。
我们的研究结果表明，hsa-miR-505是一种新的高血压循环标志物，可能在血管生成中发挥作用。我们的结果为高血压相关发病机制提供了机制性见解，并指出hsa-miR-505作为高血压干预的潜在靶点。
