Increased Density of Endogenous Adenosine A 2A Receptors in Atrial Fibrillation: From Cellular and Porcine Models to Human Patients.
Héctor Godoy-MarínVerónica Jiménez-SábadoCarmen TarifaAntonino GinelJoana Larupa Dos SantosBo Hjorth BentzenLeif Hove-MadsenFrancisco CiruelaPublished in: International journal of molecular sciences (2023)
Adenosine, an endogenous nucleoside, plays a critical role in maintaining homeostasis during stressful situations, such as energy deprivation or cellular damage. Therefore, extracellular adenosine is generated locally in tissues under conditions such as hypoxia, ischemia, or inflammation. In fact, plasma levels of adenosine in patients with atrial fibrillation (AF) are elevated, which also correlates with an increased density of adenosine A 2A receptors (A 2A Rs) both in the right atrium and in peripheral blood mononuclear cells (PBMCs). The complexity of adenosine-mediated effects in health and disease requires simple and reproducible experimental models of AF. Here, we generate two AF models, namely the cardiomyocyte cell line HL-1 submitted to Anemonia toxin II (ATX-II) and a large animal model of AF, the right atrium tachypaced pig (A-TP). We evaluated the density of endogenous A 2A R in those AF models. Treatment of HL-1 cells with ATX-II reduced cell viability, while the density of A 2A R increased significantly, as previously observed in cardiomyocytes with AF. Next, we generated the animal model of AF based on tachypacing pigs. In particular, the density of the key calcium regulatory protein calsequestrin-2 was reduced in A-TP animals, which is consistent with the atrial remodelling shown in humans suffering from AF. Likewise, the density of A 2A R in the atrium of the AF pig model increased significantly, as also shown in the biopsies of the right atrium of subjects with AF. Overall, our findings revealed that these two experimental models of AF mimicked the alterations in A 2A R density observed in patients with AF, making them attractive models for studying the adenosinergic system in AF.
Keyphrases
- atrial fibrillation
- catheter ablation
- left atrial appendage
- left atrial
- oral anticoagulants
- direct oral anticoagulants
- heart failure
- percutaneous coronary intervention
- healthcare
- endothelial cells
- escherichia coli
- end stage renal disease
- public health
- protein kinase
- chronic kidney disease
- induced apoptosis
- newly diagnosed
- gene expression
- acute coronary syndrome
- ejection fraction
- angiotensin ii
- coronary artery
- binding protein
- transcription factor