Increased Density of Endogenous Adenosine A2A Receptors in Atrial Fibrillation : From Cellular and Porcine Models to Human Patients
Godoy-Marín, Hector (Institut d'Investigació Biomèdica de Bellvitge)
Jiménez-Sábado, Verónica (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Tarifa, Carmen (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Ginel, Antonino (Institut d'Investigació Biomèdica Sant Pau)
Santos, Joana Larupa Dos (University of Copenhagen)
Bentzen, Bo Hjorth (University of Copenhagen)
Madsen, Leif Hove (Institut d'Investigació Biomèdica Sant Pau)
Ciruela, Francisco (Institut d'Investigació Biomèdica de Bellvitge)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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 receptors (ARs) 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 AR in those AF models. Treatment of HL-1 cells with ATX-II reduced cell viability, while the density of AR 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 AR 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 AR density observed in patients with AF, making them attractive models for studying the adenosinergic system in AF.
Grants:	Agencia Estatal de Investigación PID2020-118511RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1604 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1769
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	A2AR density ; AF patients ; HL-1 cells ; Adenosine A2AR receptor ; Atrial fibrillation ; Tachypaced pig
Published in:	International journal of molecular sciences, Vol. 24 Núm. 4 (february 2023) , p. 3668, ISSN 1422-0067

DOI: 10.3390/ijms24043668
PMID: 36835078

11 p, 1.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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