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Comparative and Functional Genomics logoLink to Comparative and Functional Genomics
. 2004 Aug-Oct;5(6-7):459–470. doi: 10.1002/cfg.428

Identification of a Core Set of Genes That Signifies Pathways Underlying Cardiac Hypertrophy

Claes C Strøm 1, Mogens Kruhøffer 2, Steen Knudsen 3, Frank Stensgaard-Hansen 1, Thomas E N Jonassen 4, Torben F Ørntoft 2, Stig Haunsø 1, Søren P Sheikh 1,
PMCID: PMC2447423  PMID: 18629135

Abstract

Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat

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Selected References

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  1. Agabiti-Rosei E., Muiesan M. L. Prognostic significance of left ventricular hypertrophy regression. Adv Exp Med Biol. 1997;432:199–205. doi: 10.1007/978-1-4615-5385-4_22. [DOI] [PubMed] [Google Scholar]
  2. Anversa P., Levicky V., Beghi C., McDonald S. L., Kikkawa Y. Morphometry of exercise-induced right ventricular hypertrophy in the rat. Circ Res. 1983 Jan;52(1):57–64. doi: 10.1161/01.res.52.1.57. [DOI] [PubMed] [Google Scholar]
  3. Aronow B. J., Toyokawa T., Canning A., Haghighi K., Delling U., Kranias E., Molkentin J. D., Dorn G. W., 2nd Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy. Physiol Genomics. 2001 Jun 6;6(1):19–28. doi: 10.1152/physiolgenomics.2001.6.1.19. [DOI] [PubMed] [Google Scholar]
  4. Barrans J. David, Allen Paul D., Stamatiou Dimitrios, Dzau Victor J., Liew Choong-Chin. Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. Am J Pathol. 2002 Jun;160(6):2035–2043. doi: 10.1016/S0002-9440(10)61153-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bateman A., Bennett H. P. Granulins: the structure and function of an emerging family of growth factors. J Endocrinol. 1998 Aug;158(2):145–151. doi: 10.1677/joe.0.1580145. [DOI] [PubMed] [Google Scholar]
  6. Busk Peter K., Bartkova Jirina, Strøm Claes C., Wulf-Andersen Linda, Hinrichsen Rebecca, Christoffersen Tue E. H., Latella Lucia, Bartek Jiri, Haunsø Stig, Sheikh Søren P. Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in vitro. Cardiovasc Res. 2002 Oct;56(1):64–75. doi: 10.1016/s0008-6363(02)00510-2. [DOI] [PubMed] [Google Scholar]
  7. Chien K. R., Knowlton K. U., Zhu H., Chien S. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response. FASEB J. 1991 Dec;5(15):3037–3046. doi: 10.1096/fasebj.5.15.1835945. [DOI] [PubMed] [Google Scholar]
  8. Friddle C. J., Koga T., Rubin E. M., Bristow J. Expression profiling reveals distinct sets of genes altered during induction and regression of cardiac hypertrophy. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6745–6750. doi: 10.1073/pnas.100127897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Golub T. R., Slonim D. K., Tamayo P., Huard C., Gaasenbeek M., Mesirov J. P., Coller H., Loh M. L., Downing J. R., Caligiuri M. A. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 1999 Oct 15;286(5439):531–537. doi: 10.1126/science.286.5439.531. [DOI] [PubMed] [Google Scholar]
  10. Hwang D. M., Dempsey A. A., Lee C. Y., Liew C. C. Identification of differentially expressed genes in cardiac hypertrophy by analysis of expressed sequence tags. Genomics. 2000 May 15;66(1):1–14. doi: 10.1006/geno.2000.6171. [DOI] [PubMed] [Google Scholar]
  11. Hwang Juey-Jen, Allen Paul D., Tseng George C., Lam Ching-Wan, Fananapazir Lameh, Dzau Victor J., Liew Choong-Chin. Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics. 2002 Jul 12;10(1):31–44. doi: 10.1152/physiolgenomics.00122.2001. [DOI] [PubMed] [Google Scholar]
  12. La M., D'Amico M., Bandiera S., Di Filippo C., Oliani S. M., Gavins F. N., Flower R. J., Perretti M. Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action. FASEB J. 2001 Oct;15(12):2247–2256. doi: 10.1096/fj.01-0196com. [DOI] [PubMed] [Google Scholar]
  13. Li C., Wong W. H. Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):31–36. doi: 10.1073/pnas.011404098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Liau L. M., Lallone R. L., Seitz R. S., Buznikov A., Gregg J. P., Kornblum H. I., Nelson S. F., Bronstein J. M. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Cancer Res. 2000 Mar 1;60(5):1353–1360. [PubMed] [Google Scholar]
  15. Roberts C. J., Nelson B., Marton M. J., Stoughton R., Meyer M. R., Bennett H. A., He Y. D., Dai H., Walker W. L., Hughes T. R. Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. Science. 2000 Feb 4;287(5454):873–880. doi: 10.1126/science.287.5454.873. [DOI] [PubMed] [Google Scholar]
  16. Schoenfeld J. R., Vasser M., Jhurani P., Ng P., Hunter J. J., Ross J., Jr, Chien K. R., Lowe D. G. Distinct molecular phenotypes in murine cardiac muscle development, growth, and hypertrophy. J Mol Cell Cardiol. 1998 Nov;30(11):2269–2280. doi: 10.1006/jmcc.1998.0787. [DOI] [PubMed] [Google Scholar]
  17. Sehl P. D., Tai J. T., Hillan K. J., Brown L. A., Goddard A., Yang R., Jin H., Lowe D. G. Application of cDNA microarrays in determining molecular phenotype in cardiac growth, development, and response to injury. Circulation. 2000 Apr 25;101(16):1990–1999. doi: 10.1161/01.cir.101.16.1990. [DOI] [PubMed] [Google Scholar]
  18. Stanton L. W., Garrard L. J., Damm D., Garrick B. L., Lam A., Kapoun A. M., Zheng Q., Protter A. A., Schreiner G. F., White R. T. Altered patterns of gene expression in response to myocardial infarction. Circ Res. 2000 May 12;86(9):939–945. doi: 10.1161/01.res.86.9.939. [DOI] [PubMed] [Google Scholar]
  19. Wang Wei, Xu Jinping, Kirsch Thorsten. Annexin-mediated Ca2+ influx regulates growth plate chondrocyte maturation and apoptosis. J Biol Chem. 2002 Nov 22;278(6):3762–3769. doi: 10.1074/jbc.M208868200. [DOI] [PubMed] [Google Scholar]
  20. Weinberg Ellen O., Mirotsou Maria, Gannon Joseph, Dzau Victor J., Lee Richard T., Pratt Richard E. Sex dependence and temporal dependence of the left ventricular genomic response to pressure overload. Physiol Genomics. 2003 Jan 15;12(2):113–127. doi: 10.1152/physiolgenomics.00046.2002. [DOI] [PubMed] [Google Scholar]
  21. Wollert K. C., Taga T., Saito M., Narazaki M., Kishimoto T., Glembotski C. C., Vernallis A. B., Heath J. K., Pennica D., Wood W. I. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. J Biol Chem. 1996 Apr 19;271(16):9535–9545. doi: 10.1074/jbc.271.16.9535. [DOI] [PubMed] [Google Scholar]
  22. Yang J., Moravec C. S., Sussman M. A., DiPaola N. R., Fu D., Hawthorn L., Mitchell C. A., Young J. B., Francis G. S., McCarthy P. M. Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation. 2000 Dec 19;102(25):3046–3052. doi: 10.1161/01.cir.102.25.3046. [DOI] [PubMed] [Google Scholar]

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