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Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease

Corsten, Maarten F., Dennert, Robert, Jochems, Sylvia, Kuznetsova, Tatiana, Devaux, Yvan, Hofstra, Leon, Wagner, Daniel R., Staessen, Jan A. +2 more·2010·Circulation: Cardiovascular Genetics
DOI 10.1161/circgenetics.110.957415
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Abstract

Background—: Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders. Methods and Results—: MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte–associated miR-208b and -499 were highly elevated, 1600-fold ( P <0.005) and 100-fold ( P <0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 ( P <10 −10 ) for miR-208b and 0.92 ( P <10 −9 ) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count. Conclusions—: Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation.

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  • Tissue-enriched miRNAs are increased in serum after injury to those tissues.

    “It has been demonstrated previously that tissue-enriched miRNAs are increased in serum after injury to those tissues (Corsten et al., 2010;Zhang et al., 2010).”

    From MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models (2017) · cites this paper as Corsten et al., 2010

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Authors
Corsten, M. F., Dennert, R., Jochems, S., Kuznetsova, T., Devaux, Y., Hofstra, L., Wagner, D. R., Staessen, J. A., Heymans, S., & Schroen, B.
Affiliations
From the Center for Heart Failure Research (M.F.C., R.D., S.J., S.H., B.S.), Cardiovascular Research Institute, Maastricht, The Netherlands; the Division of Hypertension and Cardiovascular Rehabilitation (T.K., J.A.S.), Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium and Department of Epidemiology, Maastricht University Medical Center, Maastricht, The Netherlands; Centre de Recherche Public–Santé, Luxembourg (Y.D., D.R.W.), Luxembourg; Maastricht University Medical...
Venue
Circulation: Cardiovascular Genetics
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-12
Volume
3
Issue
6
Pages
499-506
ISSN
  • 1942-325X
  • 1942-3268
DOI
10.1161/circgenetics.110.957415
Cited by
677
References
5
Language
en

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