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Clinical Chemistry 55: 1944-1949, 2009. First published August 20, 2009; 10.1373/clinchem.2009.125310
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(Clinical Chemistry. 2009;55:1944-1949.)
© 2009 American Association for Clinical Chemistry, Inc.

Molecular Diagnostics and Genetics

Plasma miR-208 as a Biomarker of Myocardial Injury

Xu Ji1, Rie Takahashi1, Yumiko Hiura1, Go Hirokawa1, Yasue Fukushima1 and Naoharu Iwai1,a

1 Department of Epidemiology, Research Institute, National Cardiovascular Center, Osaka, Japan.

aAddress correspondence to this author at: Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail iwai{at}ri.ncvc.go.jp.

Background: MicroRNAs (miRNAs) are endogenous small RNAs of 21–25 nucleotides that can pair with sites in 3' untranslated regions in mRNAs of protein-coding genes to downregulate their expression. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. We assessed the hypothesis that miRNAs may leak into the circulating blood from injured cells and thereby serve as biomarkers for identifying the injured cell type.

Methods: We used isoproterenol-induced myocardial injury in rats as a model and miRNA array analyses to identify candidate miRNAs specifically produced in the ventricles of the heart. Individual miRNA concentrations were measured by real-time reverse-transcription PCR. Plasma cardiac troponin I (cTnI) concentrations were measured with an ELISA.

Results: Array analyses revealed miR-208 to be produced exclusively in the heart, and we selected this miRNA as a possible biomarker of myocardial injury. Plasma concentrations of miR-208 increased significantly (P < 0.0001) after isoproterenol-induced myocardial injury and showed a similar time course to the concentration of cTnI, a classic biomarker of myocardial injury.

Conclusions: The plasma concentration of miR-208 may be a useful indicator of myocardial injury. Our results suggest that profiling of circulating miRNAs may help identify promising biomarkers of various pathologic conditions.




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