The peripheral blood mononuclear cell microRNA signature of coronary artery disease

被引:215
作者
Hoekstra, Menno [1 ]
van der Lans, Christian A. C. [1 ]
Halvorsen, Bente [3 ]
Gullestad, Lars [4 ]
Kuiper, Johan [1 ]
Aukrust, Pal [2 ,4 ]
van Berkel, Theo J. C. [1 ]
Biessen, Erik A. L. [1 ,5 ]
机构
[1] Gorlaeus Labs, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
[2] Univ Oslo, Rikshosp, Oslo Univ Hosp, Internal Med Res Inst, N-0027 Oslo, Norway
[3] Univ Oslo, Rikshosp, Dept Cardiol, N-0027 Oslo, Norway
[4] Univ Oslo, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo Univ Hosp, N-0027 Oslo, Norway
[5] Maastricht Univ, Dept Expt Vasc Pathol, Maastricht, Netherlands
关键词
Angina pectoris leukocytes; MicroRNA; Profiling; Coronary artery disease; Acute coronary syndromes; IN-VIVO; EXPRESSION; CANCER; ATHEROSCLEROSIS; MONOCYTES;
D O I
10.1016/j.bbrc.2010.03.075
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background MicroRNAs are being used in the oncology field to characterize tumors and predict the survival of cancer patients Here, we explored the potential of microRNAs as biomarkers for coronary artery disease (CAD) and acute coronary syndromes. Methods and results Using real-time PCR-based profiling, we determined the microRNA signature of peripheral blood mononuclear cells (PBMCs) from stable and unstable CAD patients and unaffected controls. 129 of 157 microRNAs measured were expressed by PBMCs and low variability between separate PBMC pools was observed The presence of CAD in general coincided with a marked 5-fold increase (P < 0 001) in the relative expression level of miR-135a, while the expression of miR-147 was 4-fold decreased (P < 0 05) in PBMCs from CAD patients as compared to controls, resulting in a 19-fold higher miR-135a/miR-147 ratio (P < 0 001) in CAD MicroRNA/target gene/biological function linkage analysis suggested that the change in PBMC microRNA signature in CAD patients is probably associated with a change in intracellular cadherin/Wnt signaling Interestingly, unstable angina pectoris patients could be discriminated from stable patients based upon their relatively high expression level of a cluster of three microRNAs including miR-198, and miR-370, suggesting that the microRNA signatures can be used to identify patients at risk for acute coronary syndromes Conclusions The present study is the first to show that microRNA signatures can possibly be utilized to identify patients exhibiting atherosclerotic CAD in general and those at risk for acute coronary syndromes. Our findings highlight the importance of microRNAs signatures as novel tool to predict clinical disease outcomes (C) 2010 Elsevier Inc All rights reserved
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页码:792 / 797
页数:6
相关论文
共 31 条
[1]   MicroRNA Signature of Malignant Mesothelioma with Potential Diagnostic and Prognostic Implications [J].
Busacca, Sara ;
Germano, Serena ;
De Cecco, Loris ;
Rinaldi, Maurizio ;
Comoglio, Federico ;
Faverot, Francesco ;
Murer, Bruno ;
Mutti, Luciano ;
Pierotti, Marco ;
Gaudino, Giovanni .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2010, 42 (03) :312-319
[2]   CD40 Expression and its Association with Low-grade Inflammation in a Greek Population of Type 1 Diabetic Juveniles: Evidence for Differences in CD40 mRNA Isoforms Expressed by Peripheral Blood Mononuclear Cells [J].
Chatzigeorgiou, A. E. ;
Lembessis, P. E. ;
Mylona-Karagianni, C. F. ;
Tsouvalas, E. A. ;
Diamanti-Kandarakis, E. ;
Kamper, E. F. .
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 2010, 118 (01) :38-46
[3]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9
[4]   MicroRNAs as regulators of mammalian hematopoiesis [J].
Chen, CZ ;
Lodish, HF .
SEMINARS IN IMMUNOLOGY, 2005, 17 (02) :155-165
[5]   Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis [J].
Cheng, AM ;
Byrom, MW ;
Shelton, J ;
Ford, LP .
NUCLEIC ACIDS RESEARCH, 2005, 33 (04) :1290-1297
[6]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P159
[7]   Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties [J].
Coulouarn, C. ;
Factor, V. M. ;
Andersen, J. B. ;
Durkin, M. E. ;
Thorgeirsson, S. S. .
ONCOGENE, 2009, 28 (40) :3526-3536
[8]   miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J].
Esau, C ;
Davis, S ;
Murray, SF ;
Yu, XX ;
Pandey, SK ;
Pear, M ;
Watts, L ;
Booten, SL ;
Graham, M ;
McKay, R ;
Subramaniam, A ;
Propp, S ;
Lollo, BA ;
Freier, S ;
Bennett, CF ;
Bhanot, S ;
Monia, BP .
CELL METABOLISM, 2006, 3 (02) :87-98
[9]   Janus kinases in immune cell signaling [J].
Ghoreschi, Kamran ;
Laurence, Arian ;
O'Shea, John J. .
IMMUNOLOGICAL REVIEWS, 2009, 228 :273-287
[10]   MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 [J].
Harris, Tamia A. ;
Yamakuchi, Munekazu ;
Ferlito, Marcella ;
Mendell, Joshua T. ;
Lowenstein, Charles J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (05) :1516-1521