Gene expression profiling during the transition to failure in TNF-α over-expressing mice demonstrates the development of autoimmune myocarditis

Zhonghua Tang, Brian S. McGowan, Sally A. Huber, Charles F. McTiernan, Sankar Addya, Saul Surrey, Toru Kubota, Paolo Fortina, Yoshihiro Higuchi, Maura A. Diamond, Dwayne S. Wyre, Arthur M. Feldman

研究成果: ジャーナルへの寄稿記事

41 引用 (Scopus)

抄録

Transgenic mice with cardiac-specific over-expression of tumor necrosis factor-α (TNF1.6) progress to dilated heart failure. A significant inflammatory response precedes functional deterioration, and may contribute to cardiac damage in this model. To evaluate the underlying molecular mechanisms, we assessed the gene expression in six groups of mouse hearts defined by age, gender, and phenotype (n = 3/group) using Affymetrix microarray analysis. Phenotype was defined as compensated (in young TNF1.6) or decompensated (in older TNF1.6) via echocardiogram. Of the >1000 transcripts altered in the compensated hearts (fold change > 2, P < 0.05 vs. wild-type (WT)), 102 were identified as immune response genes, 20 of which function in antigen presentation and processing. When comparing the compensated and decompensated hearts, >50 genes were differentially regulated, including seven immunoglobulin genes. Real-time reverse transcriptase-polymerase chain reaction and cDNA microarray confirmed the Affymetrix data. Mac3+ macrophages, CD4+ T and CD45/B220+ B-cells were identified in both compensated and decompensated hearts. However, a large amount of IgG was found deposited in areas devoid of B-lymphocytes in the myocardium of decompensated TNF1.6 mice; no such accumulation was seen in the compensated or age-matched controls. Furthermore, nuclei density analyses showed a two-fold increase in the myocardium of both compensated and decompensated TNF1.6 mice (vs. WT). This study suggests that TNF-α over-expression activates not only the inflammatory response, but also humoral immune responses within the transgenic hearts. The autoimmune response occurs concomitantly with cardiac decompensation and may participate in triggering the transition to failure in TNF1.6 mice.

元の言語英語
ページ(範囲)515-530
ページ数16
ジャーナルJournal of Molecular and Cellular Cardiology
36
発行部数4
DOI
出版物ステータス出版済み - 4 1 2004
外部発表Yes

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Myocarditis
Gene Expression Profiling
Myocardium
B-Lymphocytes
Phenotype
Immunoglobulin Genes
Microarray Analysis
Humoral Immunity
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Autoimmunity
Transgenic Mice
Real-Time Polymerase Chain Reaction
Heart Failure
Tumor Necrosis Factor-alpha
Immunoglobulin G
Macrophages
Gene Expression
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

これを引用

Gene expression profiling during the transition to failure in TNF-α over-expressing mice demonstrates the development of autoimmune myocarditis. / Tang, Zhonghua; McGowan, Brian S.; Huber, Sally A.; McTiernan, Charles F.; Addya, Sankar; Surrey, Saul; Kubota, Toru; Fortina, Paolo; Higuchi, Yoshihiro; Diamond, Maura A.; Wyre, Dwayne S.; Feldman, Arthur M.

:: Journal of Molecular and Cellular Cardiology, 巻 36, 番号 4, 01.04.2004, p. 515-530.

研究成果: ジャーナルへの寄稿記事

Tang, Z, McGowan, BS, Huber, SA, McTiernan, CF, Addya, S, Surrey, S, Kubota, T, Fortina, P, Higuchi, Y, Diamond, MA, Wyre, DS & Feldman, AM 2004, 'Gene expression profiling during the transition to failure in TNF-α over-expressing mice demonstrates the development of autoimmune myocarditis', Journal of Molecular and Cellular Cardiology, 巻. 36, 番号 4, pp. 515-530. https://doi.org/10.1016/j.yjmcc.2004.01.008
Tang, Zhonghua ; McGowan, Brian S. ; Huber, Sally A. ; McTiernan, Charles F. ; Addya, Sankar ; Surrey, Saul ; Kubota, Toru ; Fortina, Paolo ; Higuchi, Yoshihiro ; Diamond, Maura A. ; Wyre, Dwayne S. ; Feldman, Arthur M. / Gene expression profiling during the transition to failure in TNF-α over-expressing mice demonstrates the development of autoimmune myocarditis. :: Journal of Molecular and Cellular Cardiology. 2004 ; 巻 36, 番号 4. pp. 515-530.
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abstract = "Transgenic mice with cardiac-specific over-expression of tumor necrosis factor-α (TNF1.6) progress to dilated heart failure. A significant inflammatory response precedes functional deterioration, and may contribute to cardiac damage in this model. To evaluate the underlying molecular mechanisms, we assessed the gene expression in six groups of mouse hearts defined by age, gender, and phenotype (n = 3/group) using Affymetrix microarray analysis. Phenotype was defined as compensated (in young TNF1.6) or decompensated (in older TNF1.6) via echocardiogram. Of the >1000 transcripts altered in the compensated hearts (fold change > 2, P < 0.05 vs. wild-type (WT)), 102 were identified as immune response genes, 20 of which function in antigen presentation and processing. When comparing the compensated and decompensated hearts, >50 genes were differentially regulated, including seven immunoglobulin genes. Real-time reverse transcriptase-polymerase chain reaction and cDNA microarray confirmed the Affymetrix data. Mac3+ macrophages, CD4+ T and CD45/B220+ B-cells were identified in both compensated and decompensated hearts. However, a large amount of IgG was found deposited in areas devoid of B-lymphocytes in the myocardium of decompensated TNF1.6 mice; no such accumulation was seen in the compensated or age-matched controls. Furthermore, nuclei density analyses showed a two-fold increase in the myocardium of both compensated and decompensated TNF1.6 mice (vs. WT). This study suggests that TNF-α over-expression activates not only the inflammatory response, but also humoral immune responses within the transgenic hearts. The autoimmune response occurs concomitantly with cardiac decompensation and may participate in triggering the transition to failure in TNF1.6 mice.",
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AU - Tang, Zhonghua

AU - McGowan, Brian S.

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AU - McTiernan, Charles F.

AU - Addya, Sankar

AU - Surrey, Saul

AU - Kubota, Toru

AU - Fortina, Paolo

AU - Higuchi, Yoshihiro

AU - Diamond, Maura A.

AU - Wyre, Dwayne S.

AU - Feldman, Arthur M.

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