Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model

Sumeet S. Chugh, Stacey Whitesel, Mark Turner, Charles Roberts, Srinivasa R. Nagalla

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Background: We, and others, have previously reported a strong correlation between increased inter-ventricular dispersion of repolarization and the occurrence of fatal arrhythmia in animal models of CHF. The existence of this and other such distinct electrophysiologic phenotypes in right (RV) vs. left ventricles (LV) could be explained by chamber-specific patterns of gene expression. Methods: We employed microarray gene profiling of 13 824 sequence-verified, nonredundant rodent cDNAs to compare myocardial gene expression in RV vs. LV of rats with surgically induced myocardial infarction (MI: n=3) and in sham-operated animals (Sham: n=3). Results: Significant LV infarction (32±4% LV) and severe CHF were observed in all MI animals at 4 weeks. In Sham animals, 937 genes exhibited significant differential expression in RV vs. LV myocardium. In MI animals, 1158 genes exhibited significant differential expression in RV vs. LV. Of those genes exhibiting significant differential expression, only 241 were common to both Sham and MI animals. Differentially expressed genes included those involved in signal transduction, cell growth and maintenance, and apoptosis. Genes with potential roles in altered dispersion of repolarization included voltage-dependent Ca2+ channel γ subunit (MI 8-fold↑) and K+ inwardly rectifying channel subfamily J, member 10 (MI 6-fold↓). Gap junction membrane channel protein α 4 (MI 6-fold↓) and cardiac troponin I (MI 8-fold↓) were also significantly differentially expressed. Inter-ventricular comparisons revealed significantly greater alterations in gene expression vs. intra-ventricular comparisons. Conclusions: Microarray gene profiling has revealed candidate genes, some of them novel, which may account for chamber-specific ventricular electrophysiologic phenotypes, both in physiologic as well as in arrhythmogenic states such as CHF.

    Original languageEnglish (US)
    Pages (from-to)477-485
    Number of pages9
    JournalCardiovascular Research
    Volume57
    Issue number2
    DOIs
    StatePublished - Feb 1 2003

    Fingerprint

    Heart Ventricles
    Phenotype
    Genes
    Gene Expression
    Inwardly Rectifying Potassium Channel
    Connexins
    Troponin I
    Ion Channels
    Infarction
    Cardiac Arrhythmias
    Rodentia
    Signal Transduction
    Myocardium
    Membrane Proteins
    Animal Models
    Complementary DNA
    Myocardial Infarction
    Maintenance
    Apoptosis
    Growth

    Keywords

    • Arrhythmia (mechanisms)
    • Gene expression
    • Heart failure
    • Infarction
    • Ion channels
    • Repolarization
    • Sudden death

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model. / Chugh, Sumeet S.; Whitesel, Stacey; Turner, Mark; Roberts, Charles; Nagalla, Srinivasa R.

    In: Cardiovascular Research, Vol. 57, No. 2, 01.02.2003, p. 477-485.

    Research output: Contribution to journalArticle

    Chugh, Sumeet S. ; Whitesel, Stacey ; Turner, Mark ; Roberts, Charles ; Nagalla, Srinivasa R. / Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model. In: Cardiovascular Research. 2003 ; Vol. 57, No. 2. pp. 477-485.
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    abstract = "Background: We, and others, have previously reported a strong correlation between increased inter-ventricular dispersion of repolarization and the occurrence of fatal arrhythmia in animal models of CHF. The existence of this and other such distinct electrophysiologic phenotypes in right (RV) vs. left ventricles (LV) could be explained by chamber-specific patterns of gene expression. Methods: We employed microarray gene profiling of 13 824 sequence-verified, nonredundant rodent cDNAs to compare myocardial gene expression in RV vs. LV of rats with surgically induced myocardial infarction (MI: n=3) and in sham-operated animals (Sham: n=3). Results: Significant LV infarction (32±4{\%} LV) and severe CHF were observed in all MI animals at 4 weeks. In Sham animals, 937 genes exhibited significant differential expression in RV vs. LV myocardium. In MI animals, 1158 genes exhibited significant differential expression in RV vs. LV. Of those genes exhibiting significant differential expression, only 241 were common to both Sham and MI animals. Differentially expressed genes included those involved in signal transduction, cell growth and maintenance, and apoptosis. Genes with potential roles in altered dispersion of repolarization included voltage-dependent Ca2+ channel γ subunit (MI 8-fold↑) and K+ inwardly rectifying channel subfamily J, member 10 (MI 6-fold↓). Gap junction membrane channel protein α 4 (MI 6-fold↓) and cardiac troponin I (MI 8-fold↓) were also significantly differentially expressed. Inter-ventricular comparisons revealed significantly greater alterations in gene expression vs. intra-ventricular comparisons. Conclusions: Microarray gene profiling has revealed candidate genes, some of them novel, which may account for chamber-specific ventricular electrophysiologic phenotypes, both in physiologic as well as in arrhythmogenic states such as CHF.",
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    T1 - Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model

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    AU - Turner, Mark

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    AU - Nagalla, Srinivasa R.

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    AB - Background: We, and others, have previously reported a strong correlation between increased inter-ventricular dispersion of repolarization and the occurrence of fatal arrhythmia in animal models of CHF. The existence of this and other such distinct electrophysiologic phenotypes in right (RV) vs. left ventricles (LV) could be explained by chamber-specific patterns of gene expression. Methods: We employed microarray gene profiling of 13 824 sequence-verified, nonredundant rodent cDNAs to compare myocardial gene expression in RV vs. LV of rats with surgically induced myocardial infarction (MI: n=3) and in sham-operated animals (Sham: n=3). Results: Significant LV infarction (32±4% LV) and severe CHF were observed in all MI animals at 4 weeks. In Sham animals, 937 genes exhibited significant differential expression in RV vs. LV myocardium. In MI animals, 1158 genes exhibited significant differential expression in RV vs. LV. Of those genes exhibiting significant differential expression, only 241 were common to both Sham and MI animals. Differentially expressed genes included those involved in signal transduction, cell growth and maintenance, and apoptosis. Genes with potential roles in altered dispersion of repolarization included voltage-dependent Ca2+ channel γ subunit (MI 8-fold↑) and K+ inwardly rectifying channel subfamily J, member 10 (MI 6-fold↓). Gap junction membrane channel protein α 4 (MI 6-fold↓) and cardiac troponin I (MI 8-fold↓) were also significantly differentially expressed. Inter-ventricular comparisons revealed significantly greater alterations in gene expression vs. intra-ventricular comparisons. Conclusions: Microarray gene profiling has revealed candidate genes, some of them novel, which may account for chamber-specific ventricular electrophysiologic phenotypes, both in physiologic as well as in arrhythmogenic states such as CHF.

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    KW - Heart failure

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    KW - Ion channels

    KW - Repolarization

    KW - Sudden death

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