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用于检测急性心肌炎的新型循环微RNA
A Novel Circulating MicroRNA for the Detection of Acute Myocarditis


Rafael Blanco-Domínguez ... 心脑血管疾病 • 2021.05.27

NEJM生物标志物论文——基础到临床的典范

 

陈安†,颜建云†,周宏伟‡*

†南方医科大学珠江医院心脏中心;‡南方医科大学珠江医院检验医学部

*通讯作者

 

心肌炎是临床中较为常见的心血管疾病,感染、中毒、药物、自身免疫功能障碍等均可导致心肌炎的发生。诊断心肌炎通常需要排除其他疾病,其早期确诊较困难,造成真实发病率尚不清楚。目前,早期快速有效诊断心肌炎仍然是一个主要挑战。心肌活检虽然是诊断金标准,但受限于其侵入性,操作具有一定风险,临床中难以常规使用;而心脏磁共振虽然是非侵入性的,但许多医院由于设备有限而不能实施,对于危重病人也不太适合进行心脏磁共振检查。因此,寻找新的快速可靠的心肌炎诊断方法具有重要临床意义,鉴定无创和敏感的血清生物标志物将有助于心肌炎的早期诊断。

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摘要


背景

诊断急性心肌炎通常需要行心内膜心肌活检(有创)或心血管磁共振成像(未能普及)。研发更多诊断方法很有必要。我们试图确定一种用于诊断急性心肌炎的新型微RNA。

 

方法

为了确定一种对心肌炎具有特异性的微RNA,我们在小鼠中诱导实验性自身免疫性心肌炎或心肌梗死后,对分选的CD4+ T细胞和17型辅助性T(Th17)细胞进行了微RNA微阵列分析和定量聚合酶链反应(qPCR)分析。我们还在小鼠中对柯萨奇病毒诱导的心肌炎样本进行了qPCR分析。之后我们确定了这一微RNA的人类同源物,并比较了其在急性心肌炎患者血浆中和各种对照中的表达。

 

结果

我们证实,Th17细胞(特征是生成白介素-17)是心肌炎急性期的心肌损伤特征。微RNA mmu-miR-721由Th17细胞合成,存在于急性自身免疫性心肌炎或病毒性心肌炎小鼠的血浆内,但不存在于急性心肌梗死小鼠的血浆内。我们在四个独立的心肌炎患者队列中确定了人类同源物hsa-miR-Chr8:96。通过这一新型微RNA鉴别急性心肌炎患者和心肌梗死患者的接受者操作特征曲线下面积为0.927(95% CI,0.879~0.975)。在针对年龄、性别、射血分数和血清肌钙蛋白水平校正后的模型中,这一微RNA仍具有诊断价值。

 

结论

在心肌炎小鼠和患者中确定一种新型微RNA之后,我们发现,人类同源物(hsa-miR-Chr8:96)可用于鉴别心肌炎患者和心肌梗死患者(由西班牙科学和创新部[Spanish Ministry of Science and Innovation]等资助)。





作者信息

Rafael Blanco-Domínguez, M.Sc., Raquel Sánchez-Díaz, Ph.D., Hortensia de la Fuente, M.D., Ph.D., Luis J. Jiménez-Borreguero, M.D., Adela Matesanz-Marín, Ph.D., Marta Relaño, Ph.D., Rosa Jiménez-Alejandre, M.Sc., Beatriz Linillos-Pradillo, M.Sc., Katerina Tsilingiri, Ph.D., María L. Martín-Mariscal, M.D., Laura Alonso-Herranz, Ph.D., Guillermo Moreno, M.Sc., Roberto Martín-Asenjo, M.D., Marcos M. García-Guimaraes, M.D., Katelyn A. Bruno, Ph.D., Esteban Dauden, M.D., Ph.D., Isidoro González-Álvaro, M.D., Ph.D., Luisa M. Villar-Guimerans, M.D., Ph.D., Amaia Martínez-León, M.D., Ane M. Salvador-Garicano, Ph.D., Sam A. Michelhaugh, B.A., Nasrien E. Ibrahim, M.D., James L. Januzzi, M.D., Jan Kottwitz, M.D., Sabino Iliceto, M.D., Mario Plebani, M.D., Cristina Basso, M.D., Ph.D., Anna Baritussio, M.D., Ph.D., Mara Seguso, M.Sc., Renzo Marcolongo, M.D., Mercedes Ricote, Ph.D., DeLisa Fairweather, Ph.D., Héctor Bueno, M.D., Ph.D., Leticia Fernández-Friera, M.D., Ph.D., Fernando Alfonso, M.D., Ph.D., Alida L.P. Caforio, M.D., Ph.D., Domingo A. Pascual-Figal, M.D., Ph.D., Bettina Heidecker, M.D., Ph.D., Thomas F. Lüscher, M.D., Ph.D., Saumya Das, M.D., Ph.D., Valentín Fuster, M.D., Ph.D., Borja Ibáñez, M.D., Ph.D., Francisco Sánchez-Madrid, Ph.D., and Pilar Martín, Ph.D.
From the Vascular Pathophysiology Area (R.B.-D., R.S.-D., A.M.-M., M. Relaño, R.J.-A., B.L.-P., K.T., D.A.P.-F., V.F., F.S.-M., P.M.) and the Myocardial Pathophysiology Area (L.A.-H., M. Ricote, H.B., L.F.-F., B.I.), Centro Nacional de Investigaciones Cardiovasculares (CNIC), the Department of Immunology (H.F., F.S.-M.), the Department of Cardiology (L.J.J.-B., M.M.G.-G., F.A.), the Department of Dermatology (E.D.), and the Department of Rheumatology (I.G.-A.), Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Fundación Jiménez Díaz (M.L.M.-M., B.I.), the Cardiology Department, Hospital Universitario 12 de Octubre, and Instituto de Investigación Sanitaria Hospital 12 de Octubre (G.M., R.M.-A., H.B.), the Department of Immunology, Hospital Ramón y Cajal (L.M.V.-G.), HM Hospitales–Centro Integral de Enfermedades Cardiovasculares (L.F.-F.), and CIBER de Enfermedades Cardiovasculares (R.S.-D., H.F., L.J.J.-B., F.A., D.A.P.-F., B.I., F.S.-M., P.M.), Madrid, Hospital Universitario Central de Asturias, Oviedo (A.M.-L.), and the Cardiology Department, Hospital Universitario Virgen de la Arrixaca, Murcia (D.A.P.-F.) — all in Spain; the Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL (K.A.B., D.F.); the Cardiovascular Division and Corrigan Minehan Heart Center, Massachusetts General Hospital, and Harvard Medical School, Boston (A.M.S.-G., S.A.M., N.E.I., J.L.J., S.D.); Kanntonsspital St. Gallen Klinik für Anesthesiologie und Intensivmedizin, St. Gallen, Switzerland (J.K.); Cardiology (S.I., A.B., A.L.P.C.) and the Cardiovascular Pathology Unit (C.B.), the Department of Cardiac, Thoracic, Vascular Sciences and Public Health, the Department of Laboratory Medicine (M.P., M.S.), and the Department of Medicine, Hematology and Clinical Immunology (R.M.), University of Padua, Padua, Italy; Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin (B.H.); Imperial College and Royal Brompton and Harefield Hospital, London (T.F.L.); and the Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (V.F.). Address reprint requests to Dr. Martín at the Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro 3, E-28029 Madrid, Spain, or at pmartinf@cnic.es.

 

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