Combined Analysis of Human and Experimental Murine Samples Identified Novel Circulating MicroRNAs as Biomarkers for Atrial Fibrillation

  • Natsume Yu
    Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU)
  • Oaku Kasumi
    Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU)
  • Takahashi Kentaro
    Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU)
  • Nakamura Wakana
    Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU)
  • Oono Ai
    Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU)
  • Hamada Satomi
    Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU)
  • Yamazoe Masahiro
    Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU)
  • Ihara Kensuke
    Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU)
  • Sasaki Takeshi
    Heart Rhythm Center, Tokyo Medical and Dental University (TMDU)
  • Goya Masahiko
    Heart Rhythm Center, Tokyo Medical and Dental University (TMDU)
  • Hirao Kenzo
    Department of Cardiovascular Medicine, Tokyo Medical and Dental University (TMDU)
  • Furukawa Tetsushi
    Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU)
  • Sasano Tetsuo
    Department of Biofunctional Informatics, Tokyo Medical and Dental University (TMDU) Heart Rhythm Center, Tokyo Medical and Dental University (TMDU)

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<p>Background:Recent experimental studies have demonstrated that several microRNAs (miRNAs) expressed in atrial tissue promote a substrate of atrial fibrillation (AF). However, because it has not been fully elucidated whether these experimental data contribute to identifying circulating miRNAs as biomarkers for AF, we used a combined analysis of human serum and murine atrial samples with the aim of identifying these biomarkers for predicting AF.</p><p>Methods and Results:Comprehensive analyses were performed to screen 733 miRNAs in serum from 10 AF patients and 5 controls, and 672 miRNAs in atrial tissue from 6 inducible atrial tachycardia model mice and 3 controls. We selected miRNAs for which expression was detected in both analyses, and their expression levels were changed in the human analyses, the murine analyses, or both. This screening identified 11 candidate miRNAs. Next, we quantified the selected miRNAs using a quantitative RT-PCR in 50 AF and 50 non-AF subjects. The individual assessment revealed that 4 miRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were significantly upregulated in AF patients. A receiver-operating characteristics curve indicated that miR-214-3p and miR-342-5p had the highest accuracy. The combination of the 4 miRNAs modestly improved the predictive accuracy for AF (76% sensitivity, 80% specificity).</p><p>Conclusions:Novel circulating miRNAs were upregulated in the serum of AF patients and might be potential biomarkers of AF.</p>

収録刊行物

  • Circulation Journal

    Circulation Journal 82 (4), 965-973, 2018

    一般社団法人 日本循環器学会

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