Université Paris-Saclay, Inserm, UMR-S 1180, Châtenay-Malabry, France.
Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Germany; German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Germany.
J Mol Cell Cardiol. 2021 Jun;155:10-20. doi: 10.1016/j.yjmcc.2021.02.006. Epub 2021 Feb 22.
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.
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, PI3Kγ and EPAC2 were upregulated in AF. Different phosphodiesterase (PDE) families showed specific pathology-dependent changes.
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.
Genetic changes in human diseased atria.
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.
获得人正常心房和不同心脏病理状态下涉及 cAMP 信号级联的主要基因的定量表达谱。
通过 RT-qPCR 评估了在 cAMP 信号级联中起重要作用的 48 个靶基因的表达。从窦性心律（SR）伴或不伴心房扩张、阵发性心房颤动（AF）、持续性 AF 或心力衰竭（HF）患者的右心耳（RAA）和 SR 或 AF 患者的左心耳（LAA）中获得 113 个样本。我们的结果表明，供体心脏或 SR 患者的右心房和左心房附壁具有相似的表达值，除了 AC7 和 PDE2A。尽管在病理学之间基因表达变化的巨大腔依赖性变异性，但是可以识别出几个可区分的模式。AF 中 PDE8A、PI3Kγ 和 EPAC2 上调。不同的磷酸二酯酶（PDE）家族显示出特定的病理依赖性变化。
通过比较人心脏右心房和左心房附壁以及不同病理状态下 cAMP 信号级联相关基因的 mRNA 表达模式，我们表明 1）基因表达不受心脏停搏液含量的显著影响，2）使用 SR 心房样本作为对照是合适的，3）cAMP 信号级联中的许多基因在 AF 和 HF 中受到影响，但只有少数基因似乎是腔室（右或左）特异性的。
人类患病心房的遗传变化。
环腺苷酸信号通路对心房功能很重要。然而，健康和患病心脏中涉及的基因的表达模式仍不清楚。我们在此概述了不同病理状态如何影响人右心房和左心房附壁中 cAMP 信号通路关键基因的表达。我们的研究可能有助于确定新的感兴趣基因作为这些疾病的潜在治疗靶点或临床生物标志物，并可作为未来基因治疗研究的指南。
