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4 - Genomic stratification in patients with heart failure

Published online by Cambridge University Press:  05 September 2009

Tara A. Bullard
Cardiovascular Research Institute, University of Rochester Medical Centre, NY
Frédérick Aguilar
Cardiovascular Research Institute, University of Rochester Medical Centre, NY
Jennifer L. Hall
Lillehei Heart Institute, University of Minnesota, Minneapolis, MI
Burns C. Blaxall
Cardiovascular Research Institute, University of Rochester Medical Centre, NY
Wolf-Karsten Hofmann
Charite-University Hospital Benjamin Franklin, Berlin
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Cardiovascular disease, or heart failure (HF), continues to be the leading cause of death worldwide, having surpassed infectious disease in the 1990s. Current estimates indicate that chronic HF affects 1–2% of the total population of developed countries [1]. Patients with HF face a dismal prognosis: 5-year survival following diagnosis of any HF is approximately 50%, and 1-year survival for those with end-stage disease is less than 50% [2–4]. In the United States alone, there are approximately 550 000 newly diagnosed cases of HF per year, with numbers continually rising [4]. Furthermore, recent predictions suggest that HF will become the leading cause of all disability by 2020.

HF is a complex and progressive disease with numerous etiologies that involve environmental, genetic and genomic factors. While progress has been made in identifying components that may contribute to HF, our current understanding of the molecular underpinnings of HF remains remarkably limited. Although treatment modalities of recent years have improved disease prognosis, novel insights are required to enhance duration and quality of life further for patients suffering from this debilitating disease. Compounding the complex nature of HF is the recent suggestion that the adult heart expresses as many as 10 000 genes. To unravel the molecular complexities of HF, the rapidly developing field of gene expression profiling by microarrays provides an excellent means by which to investigate genome-wide difference in gene expression profiles associated with cardiovascular disease.

Gene Expression Profiling by Microarrays
Clinical Implications
, pp. 80 - 105
Publisher: Cambridge University Press
Print publication year: 2006

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Berry, C., Murdoch, D. R., and McMurray, J. J.Economics of chronic heart failure. Eur. J. Heart Fail. 2001; 3(3): 283–91.CrossRefGoogle ScholarPubMed
2001 Heart and Stroke Statistical Update. Dallas: American Heart Association; 2001.
Califf, R. M., Adams, K. F., McKenna, W. al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST). Am. Heart J. 1997; 134(1): 44–54.CrossRefGoogle Scholar
Jessup, M. and Brozena, S.Heart failure. N. Engl. J. Med. 2003; 348(20): 2007–18.CrossRefGoogle ScholarPubMed
Redfern, C. H., Degtyarev, M. Y., Kwa, A. al. Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. Proc. Natl Acad. Sci. USA 2000; 97(9): 4826–31.CrossRefGoogle Scholar
Dahlquist, K. D., Salomonis, N., Vranizan, al. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat. Genet. 2002; 31(1): 19–20.CrossRefGoogle ScholarPubMed
Aronow, B. J., Toyokawa, T., Canning, al. Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy. Physiol. Genom. 2001; 6(1): 19–28.CrossRefGoogle ScholarPubMed
Yussman, M. G., Toyokawa, T., Odley, al. Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy. Nat. Med. 2002; 8(7): 725–30.CrossRefGoogle ScholarPubMed
Narula, J., Haider, N., Virmani, al. Apoptosis in myocytes in end-stage heart failure. N. Engl. J. Med. 1996; 335(16): 1182–9.CrossRefGoogle ScholarPubMed
Communal, C., Singh, K., Pimentel, D. al. Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 1998; 98(13): 1329–34.CrossRefGoogle ScholarPubMed
Aikawa, R., Nawano, M., Gu, al. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation 2000; 102(23): 2873–9.CrossRefGoogle ScholarPubMed
Buerke, M., Murohara, T., Skurk, al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc. Natl Acad. Sci. USA 1995; 92(17): 8031–5.CrossRefGoogle ScholarPubMed
Camper-Kirby, D., Welch, S., Walker, al. Myocardial Akt activation and gender: increased nuclear activity in females versus males. Circ Res. 2001; 88(10): 1020–7.CrossRefGoogle ScholarPubMed
Matsui, T., Tao, J., del Monte, al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 2001; 104(3): 330–5.CrossRefGoogle ScholarPubMed
Matsui, T., Li, L., Wu, J. al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J. Biol. Chem. 2002; 277(25): 22896–901.CrossRefGoogle ScholarPubMed
Cook, S. A., Matsui, T., Li, al. Transcriptional effects of chronic Akt activation in the heart. J. Biol. Chem. 2002; 277(25): 22528–33.CrossRefGoogle ScholarPubMed
Kubota, T., McTiernan, C. F., Frye, C. al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ. Res. 1997; 81(4): 627–35.CrossRefGoogle ScholarPubMed
Li, Y. Y., Feng, Y. Q., Kadokami, al. Myocardial extracellular matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor alpha therapy. Proc. Natl Acad. Sci. USA 2000; 97(23): 12746–51.CrossRefGoogle ScholarPubMed
Tang, Z., McGowan, B. S., Huber, S. al. Gene expression profiling during the transition to failure in TNF-alpha over-expressing mice demonstrates the development of autoimmune myocarditis. J. Mol. Cell Cardiol. 2004; 36(4): 515–30.CrossRefGoogle ScholarPubMed
Milano, C. A., Dolber, P. C., Rockman, H. al. Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Proc. Natl Acad. Sci. USA 1994; 91(21): 10109–13.CrossRefGoogle ScholarPubMed
Wang, B. H., Du, X. J., Autelitano, D. al. Adverse effects of constitutively active alpha(1B)-adrenergic receptors after pressure overload in mouse hearts. Am. J. Physiol. Heart Circ. Physiol. 2000; 279(3): H1079–86.CrossRefGoogle ScholarPubMed
Yun, J., Zuscik, M. J., Gonzalez-Cabrera, al. Gene expression profiling of alpha(1b)-adrenergic receptor-induced cardiac hypertrophy by oligonucleotide arrays. Cardiovasc. Res. 2003; 57(2): 443–55.CrossRefGoogle ScholarPubMed
Wang, D., Oparil, S., Feng, J. al. Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide-null mouse. Hypertension 2003; 42(1): 88–95.CrossRefGoogle ScholarPubMed
Arber, S., Hunter, J. J., Ross, J. al. MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell 1997; 88(3): 393–403.CrossRefGoogle ScholarPubMed
Jones, L. R., Suzuki, Y. J., Wang, al. Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin. J. Clin. Invest. 1998; 101(7): 1385–93.CrossRefGoogle ScholarPubMed
Cho, M. C., Rapacciuolo, A., Koch, W. al. Defective beta-adrenergic receptor signaling precedes the development of dilated cardiomyopathy in transgenic mice with calsequestrin overexpression. J. Biol. Chem. 1999; 274(32): 22251–6.CrossRefGoogle ScholarPubMed
Rockman, H. A., Chien, K. R., Choi, D. al. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl Acad. Sci. USA 1998; 95(12): 7000–5.CrossRefGoogle ScholarPubMed
Blaxall, B. C., Spang, R., Rockman, H. al. Differential myocardial gene expression in the development and rescue of murine heart failure. Physiol. Genom. 2003; 15(2): 105–14.CrossRefGoogle ScholarPubMed
Ueno, S., Ohki, R., Hashimoto, al. DNA microarray analysis of in vivo progression mechanism of heart failure. Biochem. Biophys. Res. Commun. 2003; 307(4): 771–7.CrossRefGoogle ScholarPubMed
Sehl, P. D., Tai, J. T., Hillan, K. al. Application of cDNA microarrays in determining molecular phenotype in cardiac growth, development, and response to injury. Circulation 2000; 101(16): 1990–9.CrossRefGoogle ScholarPubMed
Fishbein, M. C., Maclean, D., and Maroko, P. R.Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Am. J. Pathol. 1978; 90(1): 57–70.Google ScholarPubMed
Zhao, M., Chow, A., Powers, al. Microarray analysis of gene expression after transverse aortic constriction in mice. Physiol. Genom. 2004; 19(1): 93–105.CrossRefGoogle ScholarPubMed
Wagner, R. A., Tabibiazar, R., Powers, al. Genome-wide expression profiling of a cardiac pressure overload model identifies major metabolic and signaling pathway responses. J. Mol. Cell. Cardiol. 2004; 37(6): 1159–70.CrossRefGoogle ScholarPubMed
Friddle, C. J., Koga, T., Rubin, E. al. Expression profiling reveals distinct sets of genes altered during induction and regression of cardiac hypertrophy. Proc. Natl Acad. Sci. USA 2000; 97(12): 6745–50.CrossRefGoogle ScholarPubMed
Buermans, H. P., Redout, E. M., Schiel, A. al. Micro-array analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure. Physiol. Genom. 2005.CrossRefGoogle ScholarPubMed
Lai, L. P., Lin, J. L., Lin, C. al. Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation. J. Cardiovasc. Electrophysiol. 2004; 15(2): 214–23.CrossRefGoogle ScholarPubMed
Mukherjee, S., Belbin, T. J., Spray, D. al. Microarray analysis of changes in gene expression in a murine model of chronic chagasic cardiomyopathy. Parasitol Res. 2003; 91(3): 187–96.CrossRefGoogle Scholar
Tabibiazar, R., Wagner, R. A., Liao, al. Transcriptional profiling of the heart reveals chamber-specific gene expression patterns. Circ. Res. 2003; 93(12): 1193–201.CrossRefGoogle ScholarPubMed
Chen, H. W., Yu, S. L., Chen, W. al. Dynamic changes of gene expression profiles during postnatal development of the heart in mice. Heart. 2004; 90(8): 927–34.CrossRefGoogle ScholarPubMed
Yang, J., Moravec, C. S., Sussman, M. al. Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation. 2000; 102(25): 3046–52.CrossRefGoogle ScholarPubMed
Robinson, P. A., Brown, S., McGrath, M. al. Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration. Am. J. Physiol. Cell. Physiol. 2003; 284(3): C681–95.CrossRefGoogle ScholarPubMed
Matsudaira, P. and Janmey, P.Pieces in the actin-severing protein puzzle. Cell 1988; 54(2): 139–40.CrossRefGoogle ScholarPubMed
Tan, F. L., Moravec, C. S., Li, al. The gene expression fingerprint of human heart failure. Proc. Natl Acad. Sci. USA 2002; 99(17): 11387–92.CrossRefGoogle ScholarPubMed
Barrans, J. D., Allen, P. D., Stamatiou, al. Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. Am. J. Pathol. 2002; 160(6): 2035–43.CrossRefGoogle ScholarPubMed
Schonberger, J. and Seidman, C. E.Many roads lead to a broken heart: the genetics of dilated cardiomyopathy. Am. J. Hum. Genet. 2001; 69(2): 249–60.CrossRefGoogle ScholarPubMed
Hwang, J. J., Allen, P. D., Tseng, G. al. Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol. Genom. 2002; 10(1): 31–44.CrossRefGoogle ScholarPubMed
Yung, C. K., Halperin, V. L., Tomaselli, G. al. Gene expression profiles in end-stage human idiopathic dilated cardiomyopathy: altered expression of apoptotic and cytoskeletal genes. Genomics 2004; 83(2): 281–97.CrossRefGoogle ScholarPubMed
Boheler, K. R., Volkova, M., Morrell, al. Sex- and age-dependent human transcriptome variability: implications for chronic heart failure. Proc. Natl Acad. Sci. USA 2003; 100(5): 2754–9.CrossRefGoogle ScholarPubMed
Ogletree-Hughes, M. L., Stull, L. B., Sweet, W. al. Mechanical unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in the failing human heart. Circulation 2001; 104(8): 881–6.CrossRefGoogle ScholarPubMed
Zafeiridis, A., Jeevanandam, V., Houser, S. al. Regression of cellular hypertrophy after left ventricular assist device support. Circulation 1998; 98(7): 656–62.CrossRefGoogle ScholarPubMed
Zafeiridis, A., Jeevanandam, V., Houser, S. al. Regression of cellular hypertrophy after left ventricular assist device support. Circulation 1998; 98(7): 656–62.CrossRefGoogle ScholarPubMed
Madigan, J. D., Barbone, A., Choudhri, A. al. Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device. J. Thorac. Cardiovasc. Surg. 2001; 121(5): 902–8.CrossRefGoogle ScholarPubMed
Dipla, K., Mattiello, J. A., Jeevanandam, al. Myocyte recovery after mechanical circulatory support in humans with end-stage heart failure. Circulation 1998; 97(23): 2316–22.CrossRefGoogle ScholarPubMed
Harding, J. D., Piacentino, V., 3rd, Gaughan, J. al. Electrophysiological alterations after mechanical circulatory support in patients with advanced cardiac failure. Circulation 2001; 104(11): 1241–7.CrossRefGoogle ScholarPubMed
Hosenpud, J. D., Bennett, L. E., Keck, B. al. The Registry of the International Society for Heart and Lung Transplantation: eighteenth Official Report-2001. J. Heart Lung Transpl. 2001; 20(8): 805–15.CrossRefGoogle ScholarPubMed
Rose, E. A., Gelijns, A. C., Moskowitz, A. al. Long-term use of a left-ventriuclar assist device for end-stage heart failure. N. Engl. J. Med. 2001; 345: 1435–43.CrossRefGoogle ScholarPubMed
Hetzer, R., Muller, J. H., Weng, al. Bridging-to-recovery. Ann. Thorac. Surg. 2001; 71(3 Suppl.): S109–13; discussion S114–15.CrossRefGoogle ScholarPubMed
Terracciano, C. M., Hardy, J., Birks, E. al. Clinical recovery from end-stage heart failure using left-ventricular assist device and pharmacological therapy correlates with increased sarcoplasmic reticulum calcium content but not with regression of cellular hypertrophy. Circulation 2004; 109(19): 2263–5.CrossRefGoogle Scholar
Blaxall, B. C., Tschannen-Moran, B. M., Milano, C. al. Differential gene expression and genomic patient stratification following left ventricular assist device support. J. Am. Coll. Cardiol. 2003; 41(7): 1096–106.CrossRefGoogle ScholarPubMed
Chen, Y., Park, S., Li, al. Alterations of gene expression in failing myocardium following left ventricular assist device support. Physiol. Genom. 2003; 14(3): 251–60.CrossRefGoogle ScholarPubMed
Hall, J. L., Grindle, S., Han, al. Genomic profiling of the human heart before and after mechanical support with a ventricular assist device reveals alterations in vascular signaling networks. Physiol. Genom. 2004; 17(3): 283–91.CrossRefGoogle ScholarPubMed
Huebert, R. C., Li, Q., Adhikari, al. Identification and regulation of Sprouty1, a negative inhibitor of the ERK cascade, in the human heart. Physiol. Genom. 2004; 18(3): 284–9.CrossRefGoogle ScholarPubMed
Baba, H. A., Stypmann, J., Grabellus, al. Dynamic regulation of MEK/Erks and Akt/GSK-3beta in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism. Cardiovasc. Res. 2003; 59(2): 390–9.CrossRefGoogle ScholarPubMed
Flesch, M., Margulies, K. B., Mochmann, H. al. Differential regulation of mitogen-activated protein kinases in the failing human heart in response to mechanical unloading. Circulation 2001; 104(19): 2273–6.CrossRefGoogle ScholarPubMed
Chen, M. M., Ashley, E. A., Deng, D. al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation 2003; 108(12): 1432–9.CrossRefGoogle ScholarPubMed
Ashley, E. A., Powers, J., Chen, al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc. Res. 2005; 65(1): 73–82.CrossRefGoogle ScholarPubMed
Steenbergen, C., Afshari, C. A., Petranka, J. al. Alterations in apoptotic signaling in human idiopathic cardiomyopathic hearts in failure. Am. J. Physiol. Heart Circ. Physiol. 2003; 284(1): H268–76.CrossRefGoogle ScholarPubMed
Margulies, K. B., Matiwala, S., Cornejo, al. Mixed Messages. Transcription patterns in failing and recovering human myocardium. Circ. Res. 2005.CrossRefGoogle ScholarPubMed
Kittleson, M. M., Ye, S. Q., Irizarry, R. al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 2004; 110(22): 3444–51.CrossRefGoogle ScholarPubMed
Steenman, M., Chen, Y. W., Cunff, al. Transcriptomal analysis of failing and nonfailing human hearts. Physiol Genom. 2003; 12(2): 97–112.CrossRefGoogle ScholarPubMed
Yndestad, A., Damas, J. K., Geir Eiken, al. Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure. Cardiovasc. Res. 2002; 54(1): 175–82.CrossRefGoogle ScholarPubMed
Horwitz, P. A., Tsai, E. J., Putt, M. al. Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression. Circulation 2004; 110(25): 3815–21.CrossRefGoogle ScholarPubMed
Moore, D. F., Li, H., Jeffries, al. Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke: a pilot investigation. Circulation 2005; 111(2): 212–21.CrossRefGoogle ScholarPubMed
Hill, J. M., Zalos, G., Halcox, J. al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 2003; 348(7): 593–600.CrossRefGoogle ScholarPubMed
Vasa, M., Fichtlscherer, S., Aicher, al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ. Res. 2001; 89(1): E1–7.CrossRefGoogle ScholarPubMed

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