Identification of cardiac-related circulating microRNA profile in human chronic heart failure.
Identification of cardiac-related circulating microRNA profile in human chronic heart failure.
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人类慢性心力衰竭中心脏相关循环 microRNA 谱的鉴定
DOI：
10.18632/oncotarget.6631
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发表时间：
2016-01-05
期刊：
影响因子：
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通讯作者：
Wang DW
中科院分区：
文献类型：
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作者：
Li H;Fan J;Yin Z;Wang F;Chen C;Wang DW
在慢性心力衰竭期间，循环中具有病变细胞特征的miRNA水平可以被鉴定为生物标志物。在这项研究中，我们试图确定心脏相关的循环miRNA作为心力衰竭的生物标志物。提取10例正常对照和14例慢性心力衰竭患者的血浆和心脏样本的总RNA。微阵列用于miRNA谱。通过qRT-PCR进行验证和器官/组织分布分析。此外，进行生物信息学分析以了解这些心脏相关循环miRNA在心力衰竭中的关键作用。结果显示，心脏中超过一半失调的miRNA水平在血浆中没有表现出任何差异。同时，血浆中超过90%的表达失调的miRNAs在心脏中保持稳定。在心力衰竭期间，发现四种心脏成纤维细胞来源的miRNA（miR-660- 3 p、miR-665、miR-1285- 3 p和miR-4491）在心脏和血浆中显著上调。这4个miRNAs能很好地区分患者和对照组，其中3个miRNAs与LVEF显著相关。本研究提供了血浆和衰竭心脏中miRNA变化的总体概况，并使用循环-组织miRNA概况比较模型，我们成功地鉴定了3种心脏相关循环miRNA作为诊断心力衰竭的潜在生物标志物。
During chronic heart failure, levels of circulating miRNAs endued with characteristics of diseased cells could be identified as biomarkers. In this study, we sought to identify cardiac-related circulating miRNAs as biomarkers of failing heart. Total RNA of plasma and heart samples was extracted from 10 normal controls and 14 patients with chronic heart failure. Microarray was applied for miRNA profiles. Validation and organ/tissue distribution analysis was performed by qRT-PCR. In addition, bioinformatics analysis was performed to understand the critical roles of these cardiac-related circulating miRNAs in heart failure. Results showed that levels of more than half of the miRNAs dysregulated in heart failed to show any differences in plasma. Meanwhile, more than 90% of the miRNAs dysregulated in plasma remained stable in heart. Four cardiac fibroblast-derived miRNAs (miR-660-3p, miR-665, miR-1285-3p and miR-4491) were found significantly upregulated in heart and plasma during heart failure. These 4 miRNAs strongly discriminated patients from controls, and 3 of them showed significant correlations with LVEF. This study provides global profiles of miRNAs changes in plasma and failing heart, and using a circulation-tissue miRNA profiling comparison model, we successfully identify 3 cardiac-related circulating miRNAs as potential biomarkers for diagnosis of heart failure.