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 13824 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 Ca(2+) channel gamma subunit (MI 8-fold increasing) and K(+) inwardly rectifying channel subfamily J, member 10 (MI 6-fold decreasing). Gap junction membrane channel protein alpha 4 (MI 6-fold decreasing) and cardiac troponin I (MI 8-fold decreasing) 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.
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 13824 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 Ca(2+) channel gamma subunit (MI 8-fold increasing) and K(+) inwardly rectifying channel subfamily J, member 10 (MI 6-fold decreasing). Gap junction membrane channel protein alpha 4 (MI 6-fold decreasing) and cardiac troponin I (MI 8-fold decreasing) 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.
Authors: Mark H Harpster; Somnath Bandyopadhyay; D Paul Thomas; Pavel S Ivanov; Jacque A Keele; Natalia Pineguina; Bifeng Gao; Vijay Amarendran; Mark Gomelsky; Richard J McCormick; Mark M Stayton Journal: Mamm Genome Date: 2006-07-14 Impact factor: 2.957