Circulating microRNAs are new and sensitive biomarkers of myocardial infarction

Yuri D'Alessandra, Paolo Devanna, Federica Limana, Stefania Straino, Anna Di Carlo, Paola G. Brambilla, Mara Rubino, Maria Cristina Carena, Liana Spazzafumo, Marco De Simone, Barbara Micheli, Paolo Biglioli, Felice Achilli, Fabio Martelli, Stefano Maggiolini, Giancarlo Marenzi, Giulio Pompilio, Maurizio C. Capogrossi

Research output: Contribution to journalArticle

Abstract

AimsCirculating microRNAs (miRNAs) may represent a novel class of biomarkers; therefore, we examined whether acute myocardial infarction (MI) modulates miRNAs plasma levels in humans and mice.Methods and resultsHealthy donors (n = 17) and patients (n = 33) with acute ST-segment elevation MI (STEMI) were evaluated. In one cohort (n = 25), the first plasma sample was obtained 517 ± 309 min after the onset of MI symptoms and after coronary reperfusion with percutaneous coronary intervention (PCI); miR-1, -133a, -133b, and -499-5p were ∼15- to 140-fold control, whereas miR-122 and -375 were ∼87-90 lower than control; 5 days later, miR-1, -133a, -133b, -499-5p, and -375 were back to baseline, whereas miR-122 remained lower than control through Day 30. In additional patients (n = 8; four treated with thrombolysis and four with PCI), miRNAs and troponin I (TnI) were quantified simultaneously starting 156 ± 72 min after the onset of symptoms and at different times thereafter. Peak miR-1, -133a, and -133b expression and TnI level occurred at a similar time, whereas miR-499-5p exhibited a slower time course. In mice, miRNAs plasma levels and TnI were measured 15 min after coronary ligation and at different times thereafter. The behaviour of miR-1, -133a, -133b, and -499-5p was similar to STEMI patients; further, reciprocal changes in the expression levels of these miRNAs were found in cardiac tissue 3-6 h after coronary ligation. In contrast, miR-122 and -375 exhibited minor changes and no significant modulation. In mice with acute hind-limb ischaemia, there was no increase in the plasma level of the above miRNAs.ConclusionAcute MI up-regulated miR-1, -133a, -133b, and -499-5p plasma levels, both in humans and mice, whereas miR-122 and -375 were lower than control only in STEMI patients. These miRNAs represent novel biomarkers of cardiac damage.

Original languageEnglish
Pages (from-to)2765-2773
Number of pages9
JournalEuropean Heart Journal
Volume31
Issue number22
DOIs
Publication statusPublished - Nov 2010

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Keywords

  • Circulating miRNA
  • miR-1
  • miR-133a
  • miR-133b
  • miR-499
  • Myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

D'Alessandra, Y., Devanna, P., Limana, F., Straino, S., Di Carlo, A., Brambilla, P. G., Rubino, M., Carena, M. C., Spazzafumo, L., De Simone, M., Micheli, B., Biglioli, P., Achilli, F., Martelli, F., Maggiolini, S., Marenzi, G., Pompilio, G., & Capogrossi, M. C. (2010). Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. European Heart Journal, 31(22), 2765-2773. https://doi.org/10.1093/eurheartj/ehq167