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miRNA 145 的下调和 miRNA 4516 的上调可能与原发性高血压有关。

Down-regulation of miRNA 145 and up-regulation of miRNA 4516 may be associated with primary hypertension.

机构信息

Department of Nephrology, School of Medicine, Namık Kemal University, Tekirdağ, Turkey.

Department of Nephrology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey.

出版信息

J Clin Hypertens (Greenwich). 2019 Nov;21(11):1724-1731. doi: 10.1111/jch.13704. Epub 2019 Sep 26.

Abstract

Complex mechanisms including genetic factors have been proposed in the pathogenesis of primary hypertension (HT). Micro RNAs (miRNAs) are single-stranded RNA molecules that are not converted into protein products. However, it has been established that genes regulate conversion into protein products. The primary aim of this study was to investigate the roles of miRNA 4516, miRNA 145, miRNA 24, and miRNA 181a in the pathogenesis of HT. The secondary aim was to investigate the relation between these miRNAs and renin, aldosterone, norepinephrine, renalase, and NOS. Fifty-two hypertensive and 51 control normotensive individuals under observation in the Cappadocia cohort were included in the study. miRNA 4516, miRNA 181a, miRNA 24, and miRNA 145 levels were measured using the ddPCR method. miRNA 4516 and norepinephrine levels were significantly higher in the HT group (P < .005 for both), while miRNA 145 levels were significantly lower (<.05). miRNA 4516 up-regulation (P < .05) and miRNA 145 down-regulation (P < .05) were identified as independent predictors of HT. Renalase exhibited negative correlation with miRNA 4516 and positive correlation with miRNA 145 in the patient and control group. In addition, negative correlation was present between miRNA 24 and NE and NOS and between miRNA 181a and NOS in the patient group. Our study identified, for the first time in the literature, miRNA 4516 up-regulation and miRNA 145 down-regulation as independent determinants of HT. Further studies performed in the light of our findings may lead to a better understanding of the pathogenesis and new therapeutic possibilities.

摘要

原发性高血压(HT)的发病机制中涉及复杂的机制,包括遗传因素。微 RNA(miRNA)是一种不转化为蛋白质产物的单链 RNA 分子。然而,已经确定基因调节转化为蛋白质产物。本研究的主要目的是探讨 miRNA 4516、miRNA 145、miRNA 24 和 miRNA 181a 在 HT 发病机制中的作用。次要目的是探讨这些 miRNA 与肾素、醛固酮、去甲肾上腺素、肾酶和 NOS 之间的关系。在卡帕多西亚队列中观察到的 52 例高血压和 51 例正常血压对照者被纳入本研究。使用 ddPCR 方法测量 miRNA 4516、miRNA 181a、miRNA 24 和 miRNA 145 的水平。HT 组中 miRNA 4516 和去甲肾上腺素水平显著升高(两者均 P<.005),而 miRNA 145 水平显著降低(<.05)。miRNA 4516 的上调(P<.05)和 miRNA 145 的下调(P<.05)被确定为 HT 的独立预测因子。肾酶与患者和对照组中的 miRNA 4516 呈负相关,与 miRNA 145 呈正相关。此外,在患者组中,miRNA 24 与 NE 和 NOS 之间以及 miRNA 181a 与 NOS 之间存在负相关。本研究首次在文献中确定 miRNA 4516 的上调和 miRNA 145 的下调是 HT 的独立决定因素。根据我们的发现进行的进一步研究可能会更好地了解发病机制和新的治疗可能性。

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