Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome

被引:399
作者
Widera, Christian [1 ,2 ]
Gupta, Shashi K. [3 ]
Lorenzen, Johan M. [3 ]
Bang, Claudia [3 ]
Bauersachs, Johann [2 ]
Bethmann, Kerstin [1 ,2 ]
Kempf, Tibor [1 ,2 ]
Wollert, Kai C. [1 ,2 ]
Thum, Thomas [3 ,4 ]
机构
[1] Hannover Med Sch, Div Mol & Translat Cardiol, D-30625 Hannover, Germany
[2] Hannover Med Sch, Dept Cardiol & Angiol, D-30625 Hannover, Germany
[3] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies, D-30625 Hannover, Germany
[4] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy
关键词
MicroRNAs; Acute coronary syndrome; Myocardial infarction; Prognosis; Biomarker; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; BIOMARKERS; PLASMA; EXPRESSION; HEART;
D O I
10.1016/j.yjmcc.2011.07.011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Circulating microRNAs may have diagnostic potential in acute coronary syndrome (ACS). Previous studies, however, were based on low patient numbers and could not assess the relation of microRNAs to clinical characteristics and their potential prognostic value. We thus assessed the diagnostic and prognostic value of cardiomyocyte-enriched microRNAs in the context of clinical variables and a sensitive myonecrosis biomarker in a larger ACS cohort. MiR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499 concentrations were measured by quantitative reverse transcription PCR in plasma samples obtained on admission from 444 patients with ACS. High-sensitivity troponin T (hsTnT) was measured by immunoassay. Patients were followed for 6 months regarding all-cause mortality. In a multiple linear regression analysis that included clinical variables and hsTnT, miR-1, miR-133a, miR-133b, and miR-208b were independently associated with hsTnT levels (all P<0.001). Patients with myocardial infarction presented with higher levels of miR-1, miR-133a, and miR-208b compared with patients with unstable angina. However, all six investigated microRNAs showed a large overlap between patients with unstable angina or myocardial infarction. MiR-133a and miR-208b levels were significantly associated with the risk of death in univariate and age- and gender-adjusted analyses. Both microRNAs lost their independent association with outcome upon further adjustment for hsTnT. The present study tempers speculations about the potential usefulness of cardiomyocyte-enriched microRNAs as diagnostic or prognostic markers in ACS. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:872 / 875
页数:4
相关论文
共 18 条
[1]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]   Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma [J].
Arroyo, Jason D. ;
Chevillet, John R. ;
Kroh, Evan M. ;
Ruf, Ingrid K. ;
Pritchard, Colin C. ;
Gibson, Donald F. ;
Mitchell, Patrick S. ;
Bennett, Christopher F. ;
Pogosova-Agadjanyan, Era L. ;
Stirewalt, Derek L. ;
Tait, Jonathan F. ;
Tewari, Muneesh .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (12) :5003-5008
[3]   MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice [J].
Bonauer, Angelika ;
Carmona, Guillaume ;
Iwasaki, Masayoshi ;
Mione, Marina ;
Koyanagi, Masamichi ;
Fischer, Ariane ;
Burchfield, Jana ;
Fox, Henrik ;
Doebele, Carmen ;
Ohtani, Kisho ;
Chavakis, Emmanouil ;
Potente, Michael ;
Tjwa, Marc ;
Urbich, Carmen ;
Zeiher, Andreas M. ;
Dimmeler, Stefanie .
SCIENCE, 2009, 324 (5935) :1710-1713
[4]   Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease [J].
Corsten, Maarten F. ;
Dennert, Robert ;
Jochems, Sylvia ;
Kuznetsova, Tatiana ;
Devaux, Yvan ;
Hofstra, Leon ;
Wagner, Daniel R. ;
Staessen, Jan A. ;
Heymans, Stephane ;
Schroen, Blanche .
CIRCULATION-CARDIOVASCULAR GENETICS, 2010, 3 (06) :499-506
[5]   Circulating microRNAs are new and sensitive biomarkers of myocardial infarction [J].
D'Alessandra, Yuri ;
Devanna, Paolo ;
Limana, Federica ;
Straino, Stefania ;
Di Carlo, Anna ;
Brambilla, Paola G. ;
Rubino, Mara ;
Carena, Maria Cristina ;
Spazzafumo, Liana ;
De Simone, Marco ;
Micheli, Barbara ;
Biglioli, Paolo ;
Achilli, Felice ;
Martelli, Fabio ;
Maggiolini, Stefano ;
Marenzi, Giancarlo ;
Pompilio, Giulio ;
Capogrossi, Maurizio C. .
EUROPEAN HEART JOURNAL, 2010, 31 (22) :2765-2773
[6]   Circulating MicroRNAs in Patients With Coronary Artery Disease [J].
Fichtlscherer, Stephan ;
De Rosa, Salvatore ;
Fox, Henrik ;
Schwietz, Thomas ;
Fischer, Ariane ;
Liebetrau, Christoph ;
Weber, Michael ;
Hamm, Christian W. ;
Roexe, Tino ;
Mueller-Ardogan, Marga ;
Bonauer, Angelika ;
Zeiher, Andreas M. ;
Dimmeler, Stefanie .
CIRCULATION RESEARCH, 2010, 107 (05) :677-U257
[7]   Circulating MicroRNAs as Biomarkers and Potential Paracrine Mediators of Cardiovascular Disease [J].
Gupta, Shashi K. ;
Bang, Claudia ;
Thum, Thomas .
CIRCULATION-CARDIOVASCULAR GENETICS, 2010, 3 (05) :484-488
[8]   Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR) [J].
Kroh, Evan M. ;
Parkin, Rachael K. ;
Mitchell, Patrick S. ;
Tewari, Muneesh .
METHODS, 2010, 50 (04) :298-301
[9]   Plasma MicroRNAs as Sensitive and Specific Biomarkers of Tissue Injury [J].
Laterza, Omar F. ;
Lim, Lee ;
Garrett-Engele, Philip W. ;
Vlasakova, Katerina ;
Muniappa, Nagaraja ;
Tanaka, Wesley K. ;
Johnson, Jason M. ;
Sina, Joseph F. ;
Fare, Thomas L. ;
Sistare, Frank D. ;
Glaab, Warren E. .
CLINICAL CHEMISTRY, 2009, 55 (11) :1977-1983
[10]   microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart [J].
Liu, Ning ;
Bezprozvannaya, Svetlana ;
Williams, Andrew H. ;
Qi, Xiaoxia ;
Richardson, James A. ;
Bassel-Duby, Rhonda ;
Olson, Eric N. .
GENES & DEVELOPMENT, 2008, 22 (23) :3242-3254