A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.
A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.
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DOI：
10.1056/nejmoa2003608
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发表时间：
2021-05-27
期刊：
影响因子：
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通讯作者：
Martín P
中科院分区：
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作者：
Blanco-Domínguez R;Sánchez-Díaz R;de la Fuente H;Jiménez-Borreguero LJ;Matesanz-Marín A;Relaño M;Jiménez-Alejandre R;Linillos-Pradillo B;Tsilingiri K;Martín-Mariscal ML;Alonso-Herranz L;Moreno G;Martín-Asenjo R;García-Guimaraes MM;Bruno KA;Dauden E;González-Álvaro I;Villar-Guimerans LM;Martínez-León A;Salvador-Garicano AM;Michelhaugh SA;Ibrahim NE;Januzzi JL;Kottwitz J;Iliceto S;Plebani M;Basso C;Baritussio A;Seguso M;Marcolongo R;Ricote M;Fairweather D;Bueno H;Fernández-Friera L;Alfonso F;Caforio ALP;Pascual-Figal DA;Heidecker B;Lüscher TF;Das S;Fuster V;Ibáñez B;Sánchez-Madrid F;Martín P
急性心肌炎的诊断通常需要肌内膜活检（侵入性）或心血管磁共振成像（并非普遍可用）。需要其他诊断方法。我们试图鉴定一种新的microRNA用于诊断急性心肌炎。为了鉴定心肌炎特异性microRNA，我们在诱导小鼠实验性自身免疫性心肌炎或心肌梗死后，对分选的CD 4 + T细胞和17型辅助性T细胞（Th 17）进行microRNA微阵列分析和定量聚合酶链反应（qPCR）测定。我们还对柯萨奇病毒诱导的小鼠心肌炎样品进行了qPCR。然后，我们确定了这种microRNA的人类同源物，并将其在急性心肌炎患者血浆中的表达与各种对照中的表达进行了比较。我们证实，Th 17细胞，其特征是生产白细胞介素-17，是心肌炎急性期心肌损伤的一个特征。microRNA mmu-miR-721由Th 17细胞合成，存在于急性自身免疫性或病毒性心肌炎小鼠的血浆中，但不存在于急性心肌梗死小鼠的血浆中。人类同源物，命名为hsa-miR-Chr 8：96，在四个独立的心肌炎患者队列中鉴定。这种新型microRNA用于区分急性心肌炎患者和心肌梗死患者的受试者工作特征曲线下面积为0.927（95%置信区间为0.879至0.975）。在调整年龄、性别、射血分数和血清肌钙蛋白水平后，microRNA在模型中仍保留其诊断价值。在患有心肌炎的小鼠和人类中鉴定出一种新的microRNA后，我们发现人类同源物（hsa-miR-Chr 8：96）可用于区分心肌炎患者和心肌梗死患者。（由西班牙科学与创新部等资助。
The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.)