<abstract xmlns="http://www.w3.org/1999/xhtml"> Background: Aging is associated with significantly increased prevalence of cardiac arrhythmias, but transcriptional events that underlie this process remain to be established. To gain deeper insight into molecular mechanisms of aging-related cardiac arrhythmias, we performed mRNA expression analysis comparing atrial and ventricular myocardium from Wistar-Kyoto (WKY) rats of different ages. Methods: Atrial and ventricular sampling was performed in 3 groups (n=4 each) of young (14-week-old), adult (25-week-old), and aging (47-week-old) WKY rats. mRNA expressions of 89 genes involved in cardiac arrhythmogenicity were investigated using TaqMan Low Density Array analysis. Results: Of the 89 studied genes, 40 and 64 genes presented steady atrial and ventricular expressions, respectively. All genes differentially expressed within the atria of WKY rats were up-regulated with advancing age, mainly the genes encoding for various K+, Ca2+, Na+ channels, and type 6 collagen. Atrial expression levels of 19 genes were positively correlated with age. Ventricular transcriptomic analysis revealed a balance between up-regulated and down-regulated genes encoding for the same ion channels. Conclusion: Our results indicate the induction of an up-regulation transcriptional response in atrial but not ventricular myocytes with advancing age, suggesting that the two chambers undergo different molecular remodeling programs. Aging atria displayed a transcriptomic profile consistent with higher propensity to arrhythmias, including up-regulation of genes encoding for If, ICa-L, ICa-P, INa, outward K+ currents, and collagen, while ventricular transcriptome did not seem to be significantly altered by aging. These observations could explain the higher propensity to atrial than ventricular arrhythmias in the elderly. </abstract>

Background: Aging is associated with significantly increased prevalence of cardiac arrhythmias, but transcriptional events that underlie this process remain to be established. To gain deeper insight into molecular mechanisms of aging-related cardiac arrhythmias, we performed mRNA expression analysis comparing atrial and ventricular myocardium from Wistar-Kyoto (WKY) rats of different ages. Methods: Atrial and ventricular sampling was performed in 3 groups (n=4 each) of young (14-week-old), adult (25-week-old), and aging (47-week-old) WKY rats. mRNA expressions of 89 genes involved in cardiac arrhythmogenicity were investigated using TaqMan Low Density Array analysis. Results: Of the 89 studied genes, 40 and 64 genes presented steady atrial and ventricular expressions, respectively. All genes differentially expressed within the atria of WKY rats were up-regulated with advancing age, mainly the genes encoding for various K+, Ca2+, Na+ channels, and type 6 collagen. Atrial expression levels of 19 genes were positively correlated with age. Ventricular transcriptomic analysis revealed a balance between up-regulated and down-regulated genes encoding for the same ion channels. Conclusion: Our results indicate the induction of an up-regulation transcriptional response in atrial but not ventricular myocytes with advancing age, suggesting that the two chambers undergo different molecular remodeling programs. Aging atria displayed a transcriptomic profile consistent with higher propensity to arrhythmias, including up-regulation of genes encoding for If, ICa-L, ICa-P, INa, outward K+ currents, and collagen, while ventricular transcriptome did not seem to be significantly altered by aging. These observations could explain the higher propensity to atrial than ventricular arrhythmias in the elderly.

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

Physiology Department, University of Medicine and Pharmacy of Tîrgu Mureș, 540139, Tîrgu Mureș, Romania 2. Unité de Neurocardiologie, EA4612, Université Lyon 1, F-69008, Lyon, France

Unité 1060 INSERM CarMen, Université Lyon 1, F-69008, Lyon, France

Physiology Department, University of Medicine and Pharmacy of Tîrgu Mureș, 540139, Tîrgu Mureș, Romania

Unité de Neurocardiologie, EA4612, Université Lyon 1, F-69008, Lyon, France

Unité de Neurocardiologie, EA4612, Université Lyon 1, F-69008, Lyon, France, Hospices Civils de Lyon, Hôpital Louis Pradel, Service de Rythmologie, 69500, Bron, France

Revista Romana de Medicina de Laborator

Background: Aging is associated with significantly increased prevalence of cardiac arrhythmias, but transcriptional events that underlie this process remain to...

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

Publié en ligne: 25 mars 2014

Pages: 9 - 23

DOI: https://doi.org/10.2478/rrlm-2014-0001

Mots clés
experimental model, aging, transcriptome, atrial fibrillation, ventricular arrhythmias

This content is open access.

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

Publié en ligne: 25 mars 2014

Pages: 9 - 23

DOI: https://doi.org/10.2478/rrlm-2014-0001

Mots clésexperimental model, aging, transcriptome, atrial fibrillation, ventricular arrhythmias

This content is open access.

Mots clés
experimental model, aging, transcriptome, atrial fibrillation, ventricular arrhythmias