一种细胞 microRNA，即 let-7i，是扩张型心肌病患者临床转归的新型生物标志物。

A cellular microRNA, let-7i, is a novel biomarker for clinical outcome in patients with dilated cardiomyopathy.

机构信息

Division of Cardiology, Department of Internal Medicine, and Memorial Heart Center, Iwate Medical University School of Medicine, Iwate, Japan.

出版信息

J Card Fail. 2011 Nov;17(11):923-9. doi: 10.1016/j.cardfail.2011.07.012. Epub 2011 Sep 9.

DOI:10.1016/j.cardfail.2011.07.012

PMID:22041329

Abstract

BACKGROUND

Our previous studies have reported that activation of Toll-like receptor (TLR) 4 is implicated in the etiology of human dilated cardiomyopathy (DCM). A recent report has demonstrated that let-7i, a member of the let-7 family of cellular microRNAs (miRs) miR-21, miR-126, and miR-155, directly regulate TLR4 expression. The aim of this study was to determine whether let-7i, miR-21, miR-126, and miR-155 are expressed with TLR4 in human DCM, and whether let-7i levels are related to clinical outcomes.

METHODS AND RESULTS

Endomyocardial biopsy tissues were obtained from 103 patients with DCM and 37 subjects without left ventricular (LV) dysfunction as control subjects. Levels of let-7i, miR-126, and miR-155 were lower in the DCM group than in the controls, whereas levels of miR-21 and TLR4 (both mRNA and protein) were higher in the DCM group than in the control group. Levels of let-7i were negatively correlated with TLR4 protein levels in all subjects. After a mean follow-up period of 509 days, 6 DCM patients (5.8%) had died due to a cardiac cause and 15 (14.6%) had developed heart failure. When patients with DCM were divided into tertiles according to let-7i levels, log-rank analysis showed that the DCM subgroup with low let-7i levels was associated with poor clinical outcomes (P = .02).

CONCLUSIONS

A decrease in let-7i may be related to poor clinical outcomes in patients with DCM.

摘要

背景

我们之前的研究报告称，Toll 样受体（TLR）4 的激活与人类扩张型心肌病（DCM）的病因有关。最近的一份报告表明，let-7i，细胞 microRNA（miR）miR-21、miR-126 和 miR-155 家族的一员，可直接调节 TLR4 的表达。本研究旨在确定 let-7i、miR-21、miR-126 和 miR-155 是否与 TLR4 在人类 DCM 中共同表达，以及 let-7i 水平是否与临床结局相关。

方法和结果

从 103 例 DCM 患者和 37 例无左心室（LV）功能障碍的对照者中获取心内膜心肌活检组织。DCM 组的 let-7i、miR-126 和 miR-155 水平低于对照组，而 DCM 组的 miR-21 和 TLR4（mRNA 和蛋白）水平高于对照组。在所有受试者中，let-7i 水平与 TLR4 蛋白水平呈负相关。在平均 509 天的随访后，6 例 DCM 患者（5.8%）因心脏原因死亡，15 例（14.6%）发生心力衰竭。当根据 let-7i 水平将 DCM 患者分为三分位时，log-rank 分析显示 let-7i 水平低的 DCM 亚组与不良临床结局相关（P=0.02）。