Inflammation-associated microRNA changes in circulating exosomes of heart failure patients.
Inflammation-associated microRNA changes in circulating exosomes of heart failure patients.
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DOI：
10.1186/s13104-017-3090-y
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发表时间：
2017-12-19
影响因子：
1.8
通讯作者：
Nakshatri H
中科院分区：
文献类型：
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作者：
Beg F;Wang R;Saeed Z;Devaraj S;Masoor K;Nakshatri H
MiR-486和miR-146a是富含心肌细胞的microRNAs，控制细胞存活和炎症的自我调节。这些微RNA被释放到循环中，并在血浆或循环中的外切体中被检测到。这项研究调查了心力衰竭是否会影响它们释放到循环中，目前还知之甚少。用miRVana试剂盒制备了40例心力衰竭患者和20例对照组血浆中总的和外切体特异的microRNAs。我们分别测量了外体和总血浆microRNAs，因为外体是运输生物材料和改变远处器官信号的货物，而血浆中的microRNAs表明组织损伤的程度，主要来自死亡细胞。定量RT-PCR检测miR-486、miR-146a和miR-16的表达。心力衰竭对血浆miR-486/miR-16及miR-146a/miR-16比值无明显影响，但miR-146a/miR-16有升高趋势(2.3±0.79，p=0.27)。相比之下，心力衰竭患者外周血中miR-146a/miR-16比值较高(2.46±0.51，p=0.05)。作为炎症减弱回路的一部分，MIR-146a是在炎症反应中诱导的。事实上，肿瘤坏死因子α和GM-CSF增加了心肌细胞系H9C2的miR-146a，但不增加miR-486。如果这些结果在更大的研究中得到证实，可能有助于将循环外体miR-146a发展为心力衰竭的生物标记物。
MiR-486 and miR-146a are cardiomyocyte-enriched microRNAs that control cell survival and self-regulation of inflammation. These microRNAs are released into circulation and are detected in plasma or in circulating exosomes. Little is known whether heart failure affects their release into circulation, which this study investigated. Total and exosome-specific microRNAs in plasma of 40 heart failure patients and 20 controls were prepared using the miRVana Kit. We measured exosomal and total plasma microRNAs separately because exosomes serve as cargos that transfer biological materials and alter signaling in distant organs, whereas microRNAs in plasma indicate the level of tissue damage and are mostly derived from dead cells. qRT-PCR was used to quantify miR-486, miR-146a, and miR-16. Heart failure did not significantly affect plasma miR-486/miR-16 and miR-146a/miR-16 ratio, although miR-146a/miR-16 showed a trend of elevated expression (2.3 ± 0.79, p = 0.27). By contrast, circulating exosomal miR-146a/miR-16 ratio was higher in heart failure patients (2.46 ± 0.51, p = 0.05). miR-146a is induced in response to inflammation as a part of inflammation attenuation circuitry. Indeed, Tnfα and Gm-csf increased miR-146a but not miR-486 in the cardiomyocyte cell line H9C2. These results, if confirmed in a larger study, may help to develop circulating exosomal miR-146a as a biomarker of heart failure.