Circulating miR-29a, Among Other Up-Regulated MicroRNAs, Is the Only Biomarker for Both Hypertrophy and Fibrosis in Patients With Hypertrophic Cardiomyopathy
Circulating miR-29a, Among Other Up-Regulated MicroRNAs, Is the Only Biomarker for Both Hypertrophy and Fibrosis in Patients With Hypertrophic Cardiomyopathy
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DOI：
10.1016/j.jacc.2013.09.041
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发表时间：
2014-03-11
影响因子：
24
通讯作者：
Condorelli, Gianluigi
中科院分区：
文献类型：
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作者：
Roncarati, Roberta;Anselmi, Chiara Viviani;Condorelli, Gianluigi
目的探讨肥厚型心肌病(HCM)患者外周血中参与心肌重构的microRNAs(MiRNAs)是否存在差异表达，以及循环中的miRNAs与左心室肥厚和纤维化程度是否相关。心肌miRNAs调控心肌细胞肥大、兴奋收缩偶联和细胞凋亡等过程，非CM特异性miRNAs调控心肌血管形成和纤维化。近年来，循环中的miRNAs可能是心血管疾病的生物标志物的可能性被提出。方法对41例肥厚型心肌病患者进行常规经胸超声心动图和心脏磁共振检查。结果12种miRNAs(miR-27a、-199a-5p、-26a、-145、-133a、-143、-199a-3p、-126-3p、-29a、-155、-30a和-21)在HCM血浆中显著升高。然而，只有3个miRNAs(miR-199a-5p、-27a和-29a)与肥厚相关；更重要的是，只有miR-29a与纤维化相关。结论HCM患者心脏重构决定了miRNAs的显著释放：HCM患者血浆中心脏和非心脏特异性miRNAs的循环水平均显著增加。然而，只有少数miRNAs(即miR-199a-5p、-27a和-29a)与左心室肥厚参数的相关性成立，而只有miR-29a与肥厚和纤维化两者显著相关，这表明它是评估肥厚性心肌病心肌重构的潜在生物标志物。(C)2014年，由美国心脏病学院基金会
Objectives The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis.Background miRNAs-small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation-modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised.Methods Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age-and sex-matched blood donors.Results Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis.Conclusions Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac-and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM. (C) 2014 by the American College of Cardiology Foundation