A novel circulating microRNA for the detection of acute myocarditis

Rafael Blanco-Domínguez, Raquel Sánchez-Díaz, Hortensia de la Fuente, Luis J. Jiménez-Borreguero, Adela Matesanz-Marín, Marta Relaño, Rosa Jiménez-Alejandre, Beatriz Linillos-Pradillo, Katerina Tsilingiri, María L. Martín-Mariscal, Laura Alonso-Herranz, Guillermo Moreno, Roberto Martín-Asenjo, Marcos M. García-Guimaraes, Katelyn A. Bruno, Esteban Dauden, Isidoro González-Álvaro, Luisa M. Villar-Guimerans, Amaia Martínez-León, Ane M. Salvador-GaricanoSam A. Michelhaugh, Nasrien E. Ibrahim, James L. Januzzi, Jan Kottwitz, Sabino Iliceto, Mario Plebani, Cristina Basso, Anna Baritussio, Mara Seguso, Renzo Marcolongo, Mercedes Ricote, De Lisa Fairweather, Héctor Bueno, Leticia Fernández-Friera, Fernando Alfonso, Alida L.P. Caforio, Domingo A. Pascual-Figal, Bettina Heidecker, Thomas F. Lüscher, Saumya Das, Valentín Fuster, Borja Ibáñez, Francisco Sánchez-Madrid, Pilar Martín

Research output: Contribution to journalArticlepeer-review


BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)2014-2027
Number of pages14
JournalNew England Journal of Medicine
Issue number21
StatePublished - May 27 2021

ASJC Scopus subject areas

  • Medicine(all)


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