Expression of microRNA-208 is Associated With Adverse Clinical Outcomes in Human Dilated Cardiomyopathy
Expression of microRNA-208 is Associated With Adverse Clinical Outcomes in Human Dilated Cardiomyopathy
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DOI：
10.1016/j.cardfail.2010.01.002
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发表时间：
2010-05-01
影响因子：
6
通讯作者：
Nakamura, Motoyuki
中科院分区：
文献类型：
--
作者：
Satoh, Mamoru;Minami, Yoshitaka;Nakamura, Motoyuki
背景：近年来，微RNA-208（miR-208）被广泛应用于肿瘤的治疗。肌球蛋白重链（MHC）基因，已经显示参与病理性心脏生长、纤维化和β-MHC表达的上调。最近的一项研究还报道了另外2种肌球蛋白表达的miRNA（miR-208 b和miR-499）。本研究的目的是确定是否miR-208，miR-208 b和miR-499与MHC mRNA在人类扩张型心肌病（DCM）表达，以及这些水平是否与左心室（LV）功能和临床outcomes.Methods和结果：从82例DCM患者和21例无LV功能障碍的受试者作为对照组的肌内膜活检组织中获得。DCM患者中miR-208、miR-208 b和miR-499的水平高于对照组。DCM患者的α-MHC mRNA水平低于对照组，而DCM患者的β-MHC mRNA水平高于对照组。miR-208水平与β-MHC mRNA水平和心肌胶原体积相关，而miR-208 b和miR-499水平显示无相关性。在平均517天的随访后，miR-208水平的增加被证明是临床结果的强预测因子（RR 3.4，95%CI 1.1-11.2）。结论：本研究表明，心肌miR-208的表达与DCM患者的MHC mRNA表达和不良临床结果相关。因此，我们得出结论，miR-208可能参与了人类DCM的进展。（J Cardiac Fail 2010;16：404-410）
Background: Recently, microRNA-208 (miR-208) encoded by the.-myosin heavy chain (MHC) gene, has been shown to be involved in pathological cardiac growth, fibrosis, and up-regulation of beta-MHC expression. A recent study has also reported 2 additional myosin-expressed miRNAs (miR-208b and miR-499). The aim of this study was to determine whether miR-208, miR-208b, and miR-499 are expressed with MHC mRNA in human dilated cardiomyopathy (DCM), and whether these levels are related to left ventricular (LV) function and to clinical outcomes.Methods and Results: Endomyocardial biopsy tissues were obtained from 82 patients with DCM and 21 subjects without LV dysfunction as controls. Levels of miR-208, miR-208b, and miR-499 were higher in DCM patients than in controls. Levels of alpha-MHC mRNA were lower in patients with DCM than in controls, whereas beta-MHC mRNA levels were higher in patients with DCM compared with controls. Levels of miR-208 were correlated with beta-MHC mRNA levels and myocardial collagen volume, whereas levels of miR-208b and miR-499 showed no correlation. After a mean follow-up of 517 days, an increase in miR-208 levels was shown to be a strong predictor of clinical outcomes (RR 3.4, 95% CI 1.1-11.2).Conclusions: This study suggests that myocardial expression of miR-208 is associated with MHC mRNA expression and with poor clinical outcomes in patients with DCM. We conclude that miR-208 may therefore be involved in the progression of human DCM. (J Cardiac Fail 2010;16:404-410)