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高血压患者动脉粥样硬化斑块中 microRNA-145 的过表达。

Overexpression of microRNA-145 in atherosclerotic plaques from hypertensive patients.

机构信息

G. d'Annunzio University, European Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, and Clinical Research Center, Center of Excellence on Aging (CeSI), Via dei Vestini, 66, 66100 Chieti, Italy.

出版信息

Expert Opin Ther Targets. 2013 Mar;17(3):217-23. doi: 10.1517/14728222.2013.745512. Epub 2013 Jan 23.

Abstract

BACKGROUND

MicroRNAs (miRNAs) are endogenous, non-coding, short, single-stranded RNAs and represent a new class of gene regulators. Recent evidence supports a role for miRNAs in cardiovascular pathophysiology and atherosclerosis development. We have previously demonstrated that miR-145 is widely expressed in human atherosclerotic lesions and its downregulation has been correlated with vascular smooth muscle cell dedifferentiation, a cardinal step in the development of atherosclerosis. However, no evidences are available at this time about modulation of miR-145 in the setting of hypertension. Thus, the aim of this study was to investigate the expression of miR-145 in complicated hypertension.

MATERIALS AND METHODS

Atherosclerotic plaques were obtained from 22 patients undergoing carotid endarterectomy for high-grade internal carotid artery stenosis. Plaques were subdivided into hypertension (n = 15) and control (n = 7) groups according to the presence or absence of hypertension (as defined by blood pressure > 140/90 mmHg or current antihypertensive treatment). In study plaques, miR-145 values were evaluated using real-time PCR. The level of induction has been tested by using ΔΔ cycle threshold method.

RESULTS

We found that miR-145 was significantly more expressed in atherosclerotic plaques of hypertensive patients than in control plaques (1.201 ± 0.260 vs 0.483 ± 0.148 fold induction ± SE; p = 0.026). Moreover, a post-hoc analysis showed that treatment with angiotensin receptor blockers may be associated with the maximum increase in miR-145 levels, although these data did not show any statistical significance probably due to the limited sample size.

CONCLUSIONS

To the best of our knowledge, this study is the first demonstration that hypertension may upregulate miR-145 expression in human atherosclerotic plaques. Future investigations will be necessary to establish the molecular readout of miR-145 upregulation in atherosclerotic lesions in hypertension.

摘要

背景

MicroRNAs(miRNAs)是内源性的、非编码的、短的、单链 RNA,代表了一类新的基因调控因子。最近的证据支持 miRNAs 在心血管病理生理学和动脉粥样硬化发展中的作用。我们之前已经证明,miR-145 在人类动脉粥样硬化病变中广泛表达,其下调与血管平滑肌细胞去分化相关,这是动脉粥样硬化发展的一个主要步骤。然而,目前尚无关于高血压状态下 miR-145 调节的证据。因此,本研究旨在探讨复杂高血压中 miR-145 的表达。

材料和方法

从 22 例因颈内动脉重度狭窄而行颈动脉内膜切除术的患者中获得动脉粥样硬化斑块。根据是否存在高血压(定义为血压>140/90mmHg 或正在接受降压治疗),将斑块分为高血压组(n=15)和对照组(n=7)。在研究斑块中,采用实时 PCR 评估 miR-145 的表达。采用ΔΔCt 法检测诱导水平。

结果

我们发现高血压患者的动脉粥样硬化斑块中 miR-145 的表达明显高于对照组(1.201±0.260 与 0.483±0.148 倍诱导±SE;p=0.026)。此外,一项事后分析表明,血管紧张素受体阻滞剂治疗可能与 miR-145 水平的最大增加有关,尽管由于样本量有限,这些数据没有显示出任何统计学意义。

结论

据我们所知,这是第一项证明高血压可能上调人动脉粥样硬化斑块中 miR-145 表达的研究。未来的研究将有必要确定高血压患者动脉粥样硬化病变中 miR-145 上调的分子读数。

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