Gene expression in giant cell myocarditis: Altered expression of immune response genes

Michelle M. Kittleson, Khalid M. Minhas, Rafael A. Irizarry, Shui Q. Ye, Gina Edness, Elayne Breton, John V. Conte, Gordon Tomaselli, Joe G.N. Garcia, Joshua M. Hare

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: Giant cell myocarditis is a rapidly progressive and often fatal condition without a clear etiology or treatment. A better understanding of giant cell myocarditis pathogenesis is critical to developing treatments to prevent progression and reverse damage. We compared the gene expression of giant cell myocarditis with that of nonfailing hearts. Methods: Left ventricular samples from two giant cell myocarditis patients harvested during ventricular assist device placement and six unused donor hearts were examined using Affymetrix U133A microarrays. Differential gene expression was defined with a Bonferroni-adjusted p value ≤ 0.05 from a Student's t-test and an absolute fold change ≥ 2.0. Select gene expression was confirmed with quantitative PCR. Results: Of 115 differentially expressed genes, most were upregulated in giant cell myocarditis and involved in immune response, transcriptional regulation, and metabolism. T-cell activation genes included chemokine receptor 4; chemokine ligands 5, 9, 13, and 18; interleukin-10 receptor alpha; and beta-2 integrin. Conclusions: Gene expression analysis of giant cell myocarditis offers novel insights into its pathogenesis, namely the role of T-cell activators of the Th1 subset and immune response genes previously implicated in heart failure. This forms the basis for future work aimed at defining novel therapeutic targets for giant cell myocarditis.

Original languageEnglish (US)
Pages (from-to)333-340
Number of pages8
JournalInternational Journal of Cardiology
Volume102
Issue number2
DOIs
StatePublished - Jul 10 2005

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Kittleson, M. M., Minhas, K. M., Irizarry, R. A., Ye, S. Q., Edness, G., Breton, E., Conte, J. V., Tomaselli, G., Garcia, J. G. N., & Hare, J. M. (2005). Gene expression in giant cell myocarditis: Altered expression of immune response genes. International Journal of Cardiology, 102(2), 333-340. https://doi.org/10.1016/j.ijcard.2005.03.075