Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure
Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure
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DOI：
10.1093/eurjhf/hft018
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发表时间：
2013-06-01
影响因子：
18.2
通讯作者：
van Rooij, Eva
中科院分区：
文献类型：
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作者：
Dickinson, Brent A.;Semus, Hillary M.;van Rooij, Eva
最近的研究表明，microRNAs （miRNAs）除了是基因表达的有效调节剂外，还可以作为疾病的循环生物标志物。本研究的目的是确定血浆mirna是否可以作为高血压性心脏病疾病进展或治疗效果的指标。为了确定在高血压引起的心力衰竭期间循环miRNA的变化以及对治疗的反应，我们对表现出心力衰竭迹象的高血压大鼠的血浆RNA进行了miRNA阵列。阵列分析表明，该阵列上约三分之一的mirna在血浆中可检测到。对选定的一组mirna进行定量实时聚合酶链反应（PCR）分析表明，在高血压引起的心力衰竭中，miR-16、miR-20b、miR-93、miR-106b、miR-223和miR-423-5p的循环水平显著升高，而在抗mir -208a和ACE抑制剂治疗后，这种作用减弱。此外，用anti - mir -208a治疗导致一种miRNA miR-19b的急剧增加。一项时间过程研究表明，这些miRNA中的一些变化与疾病进展有关。在高血压引起的心脏病的进展过程中，mirna的循环水平对治疗干预和变化有反应。
Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in hypertension-induced heart disease.In order to define circulating miRNAs that change during hypertension-induced heart failure and that respond to therapeutic treatment, we performed miRNA arrays on plasma RNA from hypertensive rats that show signs of heart failure. Array analysis indicated that approximately one-third of the miRNAs on the array are detectable in plasma. Quantitative real-time polymerase chain reaction (PCR) analysis for a selected panel of miRNAs indicated that circulating levels of miR-16, miR-20b, miR-93, miR-106b, miR-223, and miR-423-5p were significantly increased in response to hypertension-induced heart failure, while this effect was blunted in response to treatment with antimiR-208a as well as an ACE inhibitor. Moreover, treatment with antimiR-208a resulted in a dramatic increase in one miRNA, miR-19b. A time course study indicated that several of these miRNA changes track with disease progression.Circulating levels of miRNAs are responsive to therapeutic interventions and change during the progression of hypertension-induced heart disease.