Molecular Signatures of End-Stage Heart Failure

被引:32
作者
Lin, David [1 ,8 ]
Hollander, Zsuzsanna [1 ,8 ]
Meredith, Anna [1 ,8 ]
Stadnick, Ellamae [5 ,6 ]
Sasaki, Mayu [8 ]
Freue, Gabriela Cohen [2 ,8 ]
Qasimi, Pooran [8 ]
Mui, Alice [3 ,8 ]
Ng, Raymond T. [4 ,8 ]
Balshaw, Robert [2 ,8 ]
Wilson-McManus, Janet E. [8 ]
Wishart, David [9 ,10 ]
Hau, David [9 ]
Keown, Paul A. [5 ,8 ]
McMaster, Robert [7 ,8 ]
McManus, Bruce M. [1 ,6 ,8 ]
机构
[1] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6Z 1Y6, Canada
[2] Univ British Columbia, Dept Stat, Vancouver, BC V6Z 1Y6, Canada
[3] Univ British Columbia, Dept Surg, Vancouver, BC V6Z 1Y6, Canada
[4] Univ British Columbia, Dept Comp Sci, Vancouver, BC V6Z 1Y6, Canada
[5] Univ British Columbia, Dept Med, Vancouver, BC V6Z 1Y6, Canada
[6] Univ British Columbia, St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada
[7] Univ British Columbia, Dept Med Genet, Vancouver, BC V6Z 1Y6, Canada
[8] NCE CECR PROOF Ctr Excellence, Vancouver, BC, Canada
[9] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada
[10] Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada
关键词
Heart failure; genomics; proteomics; metabolomics; CARDIAC ALLOGRAFT-REJECTION; GENE-EXPRESSION; BIOMARKERS; GENOMICS; SYSTEM; CARDIOMYOPATHY; ABNORMALITIES; METABOLOMICS; INFLAMMATION; MECHANISMS;
D O I
10.1016/j.cardfail.2011.07.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: To date, gene expression studies related to chronic heart failure (CHF) have mainly involved microarray analysis of myocardial tissues. The potential utility of blood to infer the etiology, pathogenesis, and course of CHF remains unclear. Further, the use of proteomic and metabolomic platforms for molecular profiling of CHF is relatively unexplored. Methods: Microarray genomic, iTRAQ proteomic, and nuclear magnetic resonance metabolomic analyses were carried out on blood samples from 29 end-stage CHF patients (16 ischemic heart disease [1HD], 13 nonischemic cardiomyopathy [NICK), and 20 normal cardiac function (NCF) controls. Robust statistical tests and bioinformatical tools were applied to identify and compare the molecular signatures among these subject groups. Results: No genes or proteins, and only two metabolites, were differentially expressed between 1HD and NICM patients at end stage. However, CHF versus NCF comparison revealed differential expression of 7,426 probe sets, 71 proteins, and 8 metabolites. Functional enrichment analyses of the CHF versus NCF results revealed several in-common biological themes and potential mechanisms underlying advanced heart failure. Conclusion: Multiple "-omic" analyses support the convergence of dramatic changes in molecular processes underlying IHD and NICM at end stage. (J Cardiac Fail 2011;17:867-874)
引用
收藏
页码:867 / 874
页数:8
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