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肾动脉狭窄患者循环和肾静脉中微小RNA的水平

Circulating and renal vein levels of microRNAs in patients with renal artery stenosis.

作者信息

Park Moo Yong, Herrmann Sandra M, Saad Ahmed, Widmer Robert Jay, Tang Hui, Zhu Xiang-Yang, Lerman Amir, Textor Stephen C, Lerman Lilach O

机构信息

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.

出版信息

Nephrol Dial Transplant. 2015 Mar;30(3):480-90. doi: 10.1093/ndt/gfu341. Epub 2014 Oct 31.

Abstract

BACKGROUND

MicroRNAs (miRs) are small non-coding RNAs that are important regulators of gene expression and have been implicated in atherosclerosis. Kidney injury distal to atherosclerotic renal artery stenosis (ARAS) is aggravated by atherosclerosis. Therefore, this study tested the hypothesis that renal miR expression would be altered in patients with ARAS.

METHODS

Patients with essential hypertension (EH; n = 13) or ARAS (n = 13) underwent a 3-day protocol study under controlled conditions. For miR levels, blood samples were collected from EH and ARAS renal vein (RV) and inferior vena cava or peripheral vein of matched normotensive healthy volunteers (HV; n = 13) and patients with coronary atherosclerosis (CA; n = 11). Single-renal blood flow was measured in EH and ARAS using computer tomography to calculate renal gradients and release of miRs.

RESULTS

Glomerular filtration rate (GFR) was lower in ARAS compared with the other groups. Systemic levels of most miRs were elevated in CA. RV miR levels were lower than systemic levels in both ARAS and EH. GFR-adjusted RV levels of miR-21, 155 and 210 were reduced only in ARAS patients compared with systemic levels in HV, although cross-kidney gradients were not different from EH. RV levels of miR-21, 126, 155 and 210 correlated with GFR.

CONCLUSIONS

Levels of atherosclerosis-related miR-21, 126, 155 and 210 are decreased in the stenotic-kidney vein of ARAS compared with EH patients, likely due to decreased GFR. Yet, these miRs might be implicated in modulating renal injury in ARAS, and their RV level may be a marker reflecting their renal expression.

摘要

背景

微小RNA(miR)是小型非编码RNA,是基因表达的重要调节因子,与动脉粥样硬化有关。动脉粥样硬化性肾动脉狭窄(ARAS)远端的肾损伤会因动脉粥样硬化而加重。因此,本研究检验了ARAS患者肾miR表达会发生改变这一假设。

方法

原发性高血压(EH;n = 13)或ARAS(n = 13)患者在受控条件下进行了为期3天的方案研究。对于miR水平,从EH和ARAS肾静脉(RV)以及匹配的血压正常健康志愿者(HV;n = 13)和冠状动脉粥样硬化(CA;n = 11)患者的下腔静脉或外周静脉采集血样。使用计算机断层扫描测量EH和ARAS的单肾血流量,以计算肾梯度和miR的释放量。

结果

与其他组相比,ARAS患者的肾小球滤过率(GFR)较低。大多数miR的全身水平在CA患者中升高。ARAS和EH患者的RV miR水平均低于全身水平。与HV患者的全身水平相比,仅ARAS患者中经GFR校正的RV miR-21、155和210水平降低,尽管跨肾梯度与EH患者无差异。miR-21、126、155和210的RV水平与GFR相关。

结论

与EH患者相比,ARAS狭窄肾静脉中与动脉粥样硬化相关的miR-21、126、155和210水平降低,可能是由于GFR降低所致。然而,这些miR可能参与调节ARAS中的肾损伤,其RV水平可能是反映其肾表达的标志物。

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