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首页> 外文期刊>EBioMedicine >Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker
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Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker

机译：急性自发性冠状动脉解剖中的差分miRNA：潜在的生物标志物的病理生理洞察力

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Background Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge. Methods A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n =?15, AT-AMI n =?15), and validation cohort (SCAD n =?11, AT-AMI n =?41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays. Findings From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72–1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI. Interpretation We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition. Funding Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre.
机译：背景技术自发性冠状动脉解剖（SCAD）是急性冠状动脉综合征的重要原因，特别是年轻对中年妇女的重要原因。区分冠状动脉粥样硬化症的急性审查仍然是一个主要的临床挑战。方法采用案例对照研究探讨循环miRNA区分临床实体的有用性。使用无偏异的人RT-PCR平台评估miRNA的轮廓，并使用单独的引物证实。从两个独立的队列中评估来自急性扫描和动脉癌急性心肌梗死（AT-AMI）的血浆样品中的血浆样本中的尿染料。发现队列（SCAD n =？15，AT-AMI n =？15），验证队列（SCAD n =？11，AT-AMI n =Δ41），具有9个健康的对策。通过ELISA测定分析IL-8，TGFB1，TGBR1，内皮素-1和MMP2的血浆水平。在群组1中检测到的15个差异表达的miRNA，我们在COHORT 2中确认了4 miRNA的差异表达：miR-let-7f-5p，miR-146a-5p，miR-151a-3p和mir-223-5p，其与AMI相比，乳渣中的表达更高。与个体miRNA相比，这4 miRNA的组合表达显示了区分两个实体（AUC：0.879,95％CI 0.72-1.0）的预测值。靶基因的功能性分析鉴定了与血管生物学，TGF-β通路和细胞骨骼牵引力的关联。与AT-AMI相比，ELISA测定显示斯堪的患者中的IL-8，TGFB1，TGFBR1，内皮素-1和MMP2的高血浆水平。解释我们介绍了苏尔患者血浆miRNA的新拟合。 miR-let-7f-5p，miR-146a-5p，miR-151a-3p和mir-223-5p与AMI患者的核对鉴别备忘录，并在这种情况下的病理机制上阐明了闪光。资助西班牙经济和竞争力（Mineco）：Plan Nacional De Salue Saf2017-82886-R，Centro deInvestigaCiónBiomédicaen Red de Enfermedades心血管（Cibercv）。 FundaciónBBVAA Equipos deInvestigaciónCientífica2018年，从项目代码HR17-00016到F.S.M. Instituto de Salud Carlos III（AES 2019）：PI19 / 00565至F.R，PI19 / 00545至下午。 CAM（S2017 / BMD-3671-Inflamune-CM）来自Comunidad de Madrid到FSM和PM。英国苏德研究是由Beatscad，英国心脏基金会（BHF）PG / 13/96 / 30608 NIHR罕见疾病翻译合作和Leicester NiHR生物医学研究中心的支持。

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