Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/197204
Increased density of endogenous adenosine A2A receptors in atrial fibrillation: from cellular and porcine models to human patients
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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 A2A receptors (A2ARs) 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 A2AR in those AF models. Treatment of HL-1 cells with ATX-II reduced cell viability, while the density of A2AR 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 A2AR 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 A2AR density observed in patients with AF, making them attractive models for studying the adenosinergic system in AF.
Matèries
Matèries (anglès)
Citació
Citació
GODOY-MARÍN, Héctor, JIMÉNEZ-SÁBADO, Veronica, TARIFA, Carmen, GINEL, Antonino, LARUPA DOS SANTOS, Joana, BENTZEN, Bo hjorth, HOVE-MADSEN, Leif, CIRUELA ALFÉREZ, Francisco. Increased density of endogenous adenosine A2A receptors in atrial fibrillation: from cellular and porcine models to human patients. _International Journal of Molecular Sciences_. 2023. Vol. 24, núm. 4, pàgs. 3668. [consulta: 1 de febrer de 2026]. ISSN: 1661-6596. [Disponible a: https://hdl.handle.net/2445/197204]