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Gene expression profiling in peripheral blood nuclear cells in patients with refractory ischaemic end-stage heart failure

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Abstract

Functional analysis of up- and down-regulated genes might reveal whether peripheral blood cells may be considered as a material of diagnostic or prognostic value in patients with end-stage heart failure (HF). The aim of the present study was to compare the transcriptomic profile of peripheral blood nuclear cells from 6 male patients with ischaemic end-stage HF with those of 6 male patients with asymptomatic cardiac dysfunction. The expression of genes in peripheral blood nuclear cells in both groups of patients was measured using whole-genome oligonucleotide microarrays utilizing 35 035 oligonucleotide probes. Microarray analyses revealed 130 down-regulated genes and 15 up-regulated genes in the patients with end-stage HF. Some of the down-regulated genes belonged to the pathways that other studies have shown to be down-regulated in cardiomyopathy. We also identified up-regulated genes that have been correlated with HF severity (CXCL16) and genes involved in the regulation of expression of platelet activation factor receptor (PTAFR, RBPSUH, MCC, andPSMA7). In conclusion, the identification of genes that are differentially expressed in peripheral blood nuclear cells of patients with HF supports the suggestion that this diagnostic approach may be useful in searching for the molecular predisposition for development of severe refractory HF in patients with post-infarction asymptomatic abnormalities and remodelling of the left ventricle. These results need further investigation and validation.

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References

  • Anteby EY, Greenfield C, Natanson-Yaron S, Goldman-Wohl D, Hamani Y, Khudyak V, 2004. Vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor-4 and-10 stimulate trophoblast plasminogen activator system and metalloproteinase-9. Mol Hum Reprod 10: 229–235.

    Article  CAS  PubMed  Google Scholar 

  • Asakura M, Kitakaze M, 2009. Global gene expression profiling in the failing myocardium. Circ J 73: 1568–1576.

    Article  CAS  PubMed  Google Scholar 

  • Barrans JD, Allen PD, Stamatiou D, Dzau VJ, Liew CC, 2002. Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. Am J Pathol 160: 2035–2043.

    CAS  PubMed  Google Scholar 

  • Campo G, Valgimigli M, Gemmati D, Percoco G, Tognazzo S, Cicchitelli G, et al. 2006. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY Study. J Am Coll Cardiol 48: 2178–2185.

    Article  PubMed  Google Scholar 

  • Colak D, Kaya N, Al-Zahrani J, Al Bakheet A, Muiya P, Andres E, et al. 2009. Left ventricular global transcriptional profiling in human end-stage dilated cardiomyopathy. Genomics 94: 20–31.

    Article  CAS  PubMed  Google Scholar 

  • Dahl CP, Husberg C, Gullestad L, Waehre A, Dams JK, Vinge LE, et al. 2009. Increased production of CXCL16 in experimental and clinical heart failure: a possible role in extracellular matrix remodeling. Circ Heart Fail 2: 624–632.

    Article  CAS  PubMed  Google Scholar 

  • Ellinghaus P, Scheubel RJ, Dobrev D, Ravens U, Holtz J, Huetter J, et al. 2005. Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays. J Thorac Cardiovasc Surg 129: 1383–1390.

    Article  CAS  PubMed  Google Scholar 

  • Fox KF, Cowie MR, Wood DA, Coats AJ, Gibbs JS, Underwood SR, et al. 2001. Coronary artery disease as the cause of incident heart failure in the population. Eur Heart J 22: 228–236.

    Article  CAS  PubMed  Google Scholar 

  • Fukuyama R, Niculaita R, Ng KP, Obusez E, Sanchez J, Kalady M, et al. 2008. Mutated in colorectal cancer, a putative tumor suppressor for serrated colorectal cancer, selectively represses beta-catenin-dependent transcription. Oncogene 27: 6044–6055.

    Article  CAS  PubMed  Google Scholar 

  • Grzeskowiak R, Witt H, Drungowski M, Thermann R, Hennig S, Perrot A, et al. 2003. Expression profiling of human idiopathic dilated cardiomyopathy. Cardiovasc Res 59: 400–411.

    Article  CAS  PubMed  Google Scholar 

  • Huczek Z, Kochman J, Filipiak KJ, Horszczaruk GJ, Grabowski M, Piatkowski R, et al. 2005. Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention. J Am Coll Cardiol 46: 284–290.

    Article  PubMed  Google Scholar 

  • Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, 2005. ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 112: e154-e235.

    Article  PubMed  Google Scholar 

  • Kittleson MM, Minhas KM, Irizarry RA, Ye SQ, Edness G, Breton E, et al. 2005. Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure Physiol Genomics 2: 299–307.

    Google Scholar 

  • Kittleson MM, Ye SQ, Irizarry RA, Minhas KM, Edness G, Conte JV, et al. 2004. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation. 110: 3444–3451.

    Article  CAS  PubMed  Google Scholar 

  • Kuner R, Barth AS, Ruschhaupt M, Buness A, Zwermann L, Kreuzer E, et al. 2008. Genomic analysis reveals poor separation of human cardiomyopathies of ischemic and nonischemic etiologies. Physiol Genomics 34: 88–94.

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD, 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−δδC method. Methods 25: 402–408.

    Article  CAS  PubMed  Google Scholar 

  • MacIntyre K, Capewell S, Stewart S, Chalmers JW, Boyd J, Finlayson A, et al. 2000. Evidence of improving prognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995. Circulation 102: 1126–1131.

    CAS  PubMed  Google Scholar 

  • Massie BM, 2005. Aspirin use in chronic heart failure: what should we recommend to the practitioner? J Am Coll Cardiol 46: 963–966.

    Article  CAS  PubMed  Google Scholar 

  • McDonagh TA, Morrison CE, Lawrence A, Ford I, Tunstall-Pedoe H, McMurray JJ, et al. 1997. Symptomatic and asymptomatic left ventricular systolic dysfunction in an urban population. Lancet 350: 829–833.

    Article  CAS  PubMed  Google Scholar 

  • Nachman RL, Rafii S, 2008. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med 359: 1261–1270.

    Article  CAS  PubMed  Google Scholar 

  • Rajan S, Williams SS, Jagatheesan G, Ahmed RP, Fuller-Bicer G, Schwartz A, et al. 2006. Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy. Physiol Genomics 27: 309–317.

    Article  CAS  PubMed  Google Scholar 

  • Ruppert V, Meyer T, Pankuweit S, Moller E, Funck RC, Grimm W, et al. 2008. Gene expression profiling from endomycardial biopsy tissue allows distinction between subentities of dilated cardiomyopathy. J Thorac Cardiovasc Surg 136: 360–369.e1.

    Article  CAS  PubMed  Google Scholar 

  • Sanoudou D, Vafiadaki E, Arvantilis DA, Kranias E, Kontrogianni-Konstantopoulos A, 2005. Array lessons from heart: focus on genome and transcriptome of cardiomyopathies. Physiol Genomics 21: 131–143.

    Article  CAS  PubMed  Google Scholar 

  • Schaufelberger M, Swedberg K, Köster M, Rosén M, Rosengren A, 2004. Decreasing one-year mortality and hospitalization rates for heart failure in Sweden; data from the Swedish Hospital Discharge Registry 1988 to 2000. Eur Heart J 25: 300–307.

    Article  PubMed  Google Scholar 

  • Simon RM, Dobbin K, 2003. Experimental design of DNA microarray experiments. Biotechniques 34: S16-S21.

    Google Scholar 

  • Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJ, 2001. More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 3: 315–322.

    Article  CAS  PubMed  Google Scholar 

  • Tan FL, Moravec CS, Li J, Apperson-Hansen C, Mc-Carthy PM, Toung JB, et al. 2002. The gene expression fingerprint of human heart failure. Proc Natl Acad Sci U S A 99: 11387–11392.

    Article  CAS  PubMed  Google Scholar 

  • Tang Y, Urs S, Liaw L, 2008. Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site. Circ Res 102: 661–668.

    Article  CAS  PubMed  Google Scholar 

  • Thomas PD, Kejariwal A, Campbell MJ, Mi H, Diemer K, Guo N, et al. 2003. PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification. Nucleic Acids Res 31: 334–341.

    Article  CAS  PubMed  Google Scholar 

  • Wang TJ, Evans JC, Benjamin EJ, Levy D, LeRoy EC, Vasan RS, 2003. Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation 108: 977–982.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. First Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097, Warsaw, Poland

    S. Szmit, M. Grabowski, R. Glowczynska, A. Majewska, K. J. Filipiak & G. Opolski

  2. Department of Oncology, Military Institute of Medicine, Warsaw, Poland

    S. Szmit

  3. Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland

    M. Jank & T. Motyl

  4. Institute of Computer Engineering, Control and Robotics (1-6), Wrocław University of Technology, Wrocław, Poland

    H. Maciejewski

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  1. S. Szmit
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  2. M. Jank
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  3. H. Maciejewski
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  4. M. Grabowski
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  5. R. Glowczynska
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  6. A. Majewska
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  9. G. Opolski
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Correspondence to S. Szmit.

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Szmit, S., Jank, M., Maciejewski, H. et al. Gene expression profiling in peripheral blood nuclear cells in patients with refractory ischaemic end-stage heart failure. J Appl Genet 51, 353–368 (2010). https://doi.org/10.1007/BF03208866

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  • DOI: https://doi.org/10.1007/BF03208866

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