The distribution of circulating microRNA and their relation to coronary disease.
The distribution of circulating microRNA and their relation to coronary disease.
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DOI：
10.12688/f1000research.1-50.v1
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Tanriverdi K
中科院分区：
文献类型：
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作者：
Freedman JE;Ercan B;Morin KM;Liu CT;Tamer L;Ayaz L;Kanadasi M;Cicek D;Seyhan AI;Akilli RE;Camci C;Cengiz B;Oztuzcu S;Tanriverdi K
背景：微小RNA（microRNAs，miRNAs）是一类通过抑制蛋白质翻译来调节基因表达的小分子RNA，可能影响RNA的表达。microRNA在细胞外位置如血浆中被检测到;然而，血浆中miRNA表达的程度及其与心血管疾病的关系尚不清楚，许多临床研究利用了基于阵列的平台，其重现性较差。 方法和结果：最初，为了确定miRNA在人血液中的分布;使用高通量微流体定量RT-PCR（qRT-PCR）筛选来自5个正常个体的全血、血小板、单核细胞、血浆和血清中的852种miRNA。共计;发现609、448、658、147和178个miRNA分别在全血、血小板、单核细胞、血浆和血清中以中等至高水平表达，其中一些miRNA独特地表达。为了确定血液miRNA表达的心血管相关性，在83名进行心导管插入术的患者中测量血浆miRNA（n=852）水平。与轻微冠状动脉疾病（狭窄小于70%）或正常冠状动脉相比，8种血浆miRNA在严重冠状动脉疾病（狭窄≥70%）患者中的表达增加2倍以上。发现miR-494、miR-490- 3 p和miR-769- 3 p的表达具有显著不同的表达水平。使用包括心血管危险因素和药物的多变量回归模型，发现hsa-miR-769- 3 p与显著冠状动脉粥样硬化的存在显著相关。 结论：本研究利用了一种基于上级高通量qRT-PCR的方法，发现miRNA在人血液中广泛表达，在细胞和细胞外组分之间表达存在差异。重要的是，来自循环血浆的特异性miRNA与显著冠状动脉疾病的存在相关。
Background: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility. Methods and Results: Initially, to define distribution of miRNA in human blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis. Conclusions: This study utilized a superior high-throughput qRT-PCR based method and found that miRNAs are found to be widely expressed in human blood with differences expressed between cellular and extracellular fractions. Importantly, specific miRNAs from circulating plasma are associated with the presence of significant coronary disease.