A Cellular MicroRNA, let-7i, Is a Novel Biomarker for Clinical Outcome in Patients With Dilated Cardiomyopathy

BackgroundOur 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 ResultsEndomyocardial 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).ConclusionsA decrease in let-7i may be related to poor clinical outcomes in patients with DCM.