Circulating MicroRNAs as Novel Potential Biomarkers for Left Ventricular Remodeling in Postinfarction Heart Failure
Circulating MicroRNAs as Novel Potential Biomarkers for Left Ventricular Remodeling in Postinfarction Heart Failure
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循环 MicroRNA 作为梗死后心力衰竭左心室重构的新型潜在生物标志物
DOI：
10.1155/2019/5093803
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发表时间：
2019-12-02
期刊：
影响因子：
--
通讯作者：
Yang, Ping
中科院分区：
文献类型：
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作者：
Gao, Guangyuan;Chen, Weiwei;Yang, Ping
循环microRNAs （miRNAs）被认为是梗死后心力衰竭（HF）左心室重构的潜在生物标志物。然而，使用循环mirna的诊断可重复性可能受到心肌梗死（MI）后mirna时间表达的影响。在目前的研究中，我们使用心肌梗死诱导的HF大鼠队列（心肌梗死后4周、8周和12周组），研究了左心室重构发展过程中血浆mirna的时间表达。通过miRNA测序获得血浆miRNA表达谱。real-time PCR检测候选mirna在血浆和组织中的表达。使用平行mirna -信使RNA表达谱方法预测候选mirna的靶基因。采用实时荧光定量PCR技术评估血浆mirna作为左心室重构生物标志物在梗死后HF患者（n = 32）和稳定型心绞痛且无明显冠状动脉病变和HF的对照患者（n = 16）中的价值。尽管miR-20a-5p、miR-340-5p和let-7i-5p在血浆、心肌和外周血单个核细胞中的表达水平暂时受到调节，但血浆mirna的表达水平，尤其是miR-20a-5p，与梗死后HF大鼠左室重构的发展有关。这3种mirna的靶基因与雷帕霉素、核因子-κB、肿瘤坏死因子、细胞凋亡和p53信号通路的机制靶点相关。此外，梗死后HF患者血浆miR-20a-5p、miR-340-5p和let-7i-5p水平显著升高。然而，只有miR-20a-5p的表达水平与左室舒张末期内径和左室舒张末期容积呈显著正相关。综上所述，血浆miR-20a-5p表达水平与左室扩张程度显著相关，血浆miR-20a-5p可能是梗死后左室重构的潜在生物标志物。
Circulating microRNAs (miRNAs) have been proposed as potential biomarkers for left ventricular remodeling in postinfarction heart failure (HF). However, the diagnostic reproducibility of the use of circulating miRNAs may be affected by the temporal expression of miRNAs following myocardial infarction (MI). In the current study, using a MI-induced HF rat cohort (4-, 8-, and 12-week post-MI groups), we investigated the temporal expression of plasma miRNAs during the development of left ventricular remodeling. The plasma miRNA expression profile was obtained using miRNA sequencing. The expression of candidate miRNAs in plasma and tissues was examined with real-time PCR. Target genes of candidate miRNAs were predicted using a parallel miRNA-messenger RNA expression profiling approach. The value of plasma miRNAs as biomarkers for left ventricular remodeling was evaluated in patients with postinfarction HF (n = 32) and control patients with stable angina and without significant coronary lesions and HF (n = 16) with real-time PCR. Although the expression levels of miR-20a-5p, miR-340-5p, and let-7i-5p were temporally regulated in plasma, myocardium, and peripheral blood mononuclear cells, the expression levels of plasma miRNAs, especially miR-20a-5p, were associated with the development of left ventricular remodeling in the postinfarction HF rat cohort. The target genes of these 3 miRNAs were associated with the mechanistic target of rapamycin, nuclear factor-κB, tumour necrosis factor, apoptosis, and p53 signaling pathways. Additionally, the plasma levels of miR-20a-5p, miR-340-5p, and let-7i-5p were significantly increased in patients with postinfarction HF. However, only the expression levels of miR-20a-5p presented significant positive correlations with left ventricular internal end diastolic dimension and left ventricular end diastolic volume. In conclusion, the expression levels of plasma miR-20a-5p were significantly associated with the degree of left ventricular dilatation, and plasma miR-20a-5p may be a potential biomarker for postinfarction left ventricular remodeling.