Garnier, Anne and Bork, Nadja and Jacquet, Eric and Zipfel, Svante and Munoz-Guijosa, Christian and Baczko, Istvan and Reichenspurner, Hermann and Donzeau-Gouge, Patrick and Maier, Lars S. and Dobrev, Dobromir and Girdauskas, Evaldas and Nikolaev, Viacheslav O. and Fischmeister, Rodolphe and Molina, Cristina E. (2021) Mapping genetic changes in the cAMP-signaling cascade in human atria. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 155. pp. 10-20. ISSN 0022-2828, 1095-8584
Full text not available from this repository. (Request a copy)Abstract
Aim: To obtain a quantitative expression profile of the main genes involved in the cAMP-signaling cascade in human control atria and in different cardiac pathologies. Methods and results: Expression of 48 target genes playing a relevant role in the cAMP-signaling cascade was assessed by RT-qPCR. 113 samples were obtained from right atrial appendages (RAA) of patients in sinus rhythm (SR) with or without atrium dilation, paroxysmal atrial fibrillation (AF), persistent AF or heart failure (HF); and left atrial appendages (LAA) from patients in SR or with AF. Our results show that right and left atrial appendages in donor hearts or from SR patients have similar expression values except for AC7 and PDE2A. Despite the enormous chamber-dependent variability in the gene-expression changes between pathologies, several distinguishable patterns could be identified. PDE8A, PI3K gamma and EPAC2 were upregulated in AF. Different phosphodiesterase (PDE) families showed specific pathology-dependent changes. Conclusion: By comparing mRNA-expression patterns of the cAMP-signaling cascade related genes in right and left atrial appendages of human hearts and across different pathologies, we show that 1) gene expression is not significantly affected by cardioplegic solution content, 2) it is appropriate to use SR atrial samples as controls, and 3) many genes in the cAMP-signaling cascade are affected in AF and HF but only few of them appear to be chamber (right or left) specific. Topic: Genetic changes in human diseased atria. Translational perspective: The cyclic AMP signaling pathway is important for atrial function. However, expression patterns of the genes involved in the atria of healthy and diseased hearts are still unclear. We give here a general overview of how different pathologies affect the expression of key genes in the cAMP signaling pathway in human right and left atria appendages. Our study may help identifying new genes of interest as potential therapeutic targets or clinical biomarkers for these pathologies and could serve as a guide in future gene therapy studies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN HEART-FAILURE; CYCLIC-NUCLEOTIDES; DOWN-REGULATION; EXPORT PUMP; AKAP-LBC; I-KS; EXPRESSION; RESISTANCE; FIBRILLATION; EPAC; Atrial fibrillation; Heart failure; Right atria; Left atria; cAMP-signaling cascade; beta-Adrenergic pathway |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 11:44 |
| Last Modified: | 21 Sep 2022 11:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47856 |
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