Serum levels of microRNAs in patients with heart failure

被引:295
作者
Goren, Yaron [3 ]
Kushnir, Michal [3 ]
Zafrir, Barak [1 ,2 ]
Tabak, Sarit [3 ]
Lewis, Basil S. [1 ,2 ]
Amir, Offer [1 ,2 ]
机构
[1] Technion Israel Inst Technol, Dept Cardiovasc Med, Lady Davis Carmel Med Ctr, Haifa, Israel
[2] Technion Israel Inst Technol, Heart Failure Clin, Lin Med Ctr, Bruce & Ruth Rappaport Fac Med, Haifa, Israel
[3] Rosetta Genom Ltd, Rehovot, Israel
关键词
Biomarkers; Heart failure; MicroRNA; CIRCULATING MICRORNAS; MYOCARDIAL-INFARCTION; EXPRESSION; DISEASE; PLASMA; CARDIOMYOPATHY; ANGIOTENSIN; PHENOTYPE; SIGNATURE; BIOMARKER;
D O I
10.1093/eurjhf/hfr155
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims Diagnosis and risk stratification of patients with heart failure remain a challenge. The small non-coding RNAs known as microRNAs regulate gene expression and seem to play an important role in the pathogenesis of heart failure. In the current study, we aim to characterize the levels of microRNAs in the sera of chronic systolic heart failure patients vs. controls and assess the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in heart failure patients. Methods and results The levels of 186 microRNAs were measured in the sera of 30 stable chronic systolic heart failure patients and 30 controls using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The differences in microRNA levels between the two groups were characterized, and a score, based on the levels of four specific microRNAs with the most significant increase in the heart failure group (miR-423-5p, miR-320a, miR-22, and miR-92b), was defined. The score was used to discriminate heart failure patients from controls with a sensitivity and specificity of 90%. Moreover, in the heart failure group, there was a significant association between the score and important clinical prognostic parameters such as elevated serum natriuretic peptide levels, a wide QRS, and dilatation of the left ventricle and left atrium (r = 0.63, P = 3e-4; P = 0.009; P = 0.03; and P = 0.01, respectively). Conclusions Elevated serum levels of specific microRNAs: miR-423-5p, miR-320a, miR-22, and miR-92b, identify systolic heart failure patients and correlate with important clinical prognostic parameters.
引用
收藏
页码:147 / 154
页数:8
相关论文
共 34 条
[1]  
Amir RE, 2008, GENET MED, V10, P593, DOI [10.1097/GIM.0b013e3181804b9c, 10.1097GIM.0b013e3181804b9c]
[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]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[5]   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
[6]   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
[7]   miR-133 and miR-30 Regulate Connective Tissue Growth Factor Implications for a Role of MicroRNAs in Myocardial Matrix Remodeling [J].
Duisters, Rudy F. ;
Tijsen, Anke J. ;
Schroen, Blanche ;
Leenders, Joost J. ;
Lentink, Viola ;
van der Made, Ingeborg ;
Herias, Veronica ;
van Leeuwen, Rick E. ;
Schellings, Mark W. ;
Barenbrug, Paul ;
Maessen, Jos G. ;
Heymans, Stephane ;
Pinto, Yigal M. ;
Creemers, Esther E. .
CIRCULATION RESEARCH, 2009, 104 (02) :170-U61
[8]   Assessment of Plasma miRNAs in Congestive Heart Failure [J].
Fukushima, Yasue ;
Nakanishi, Michio ;
Nonogi, Hiroshi ;
Goto, Yoichi ;
Iwai, Naoharu .
CIRCULATION JOURNAL, 2011, 75 (02) :336-340
[9]   Cardiospecific microRNA Plasma Levels Correlate with Troponin and Cardiac Function in Patients with ST Elevation Myocardial Infarction, Are Selectively Dependent on Renal Elimination, and Can Be Detected in Urine Samples [J].
Gidlof, Olof ;
Andersson, Patrik ;
van der Pals, Jesper ;
Gotberg, Matthias ;
Erlinge, David .
CARDIOLOGY, 2011, 118 (04) :217-226
[10]   Serum MicroRNAs Are Promising Novel Biomarkers [J].
Gilad, Shlomit ;
Meiri, Eti ;
Yogev, Yariv ;
Benjamin, Sima ;
Lebanony, Danit ;
Yerushalmi, Noga ;
Benjamin, Hila ;
Kushnir, Michal ;
Cholakh, Hila ;
Melamed, Nir ;
Bentwich, Zvi ;
Hod, Moshe ;
Goren, Yaron ;
Chajut, Ayelet .
PLOS ONE, 2008, 3 (09)