Adenosine A2A Receptors Are Upregulated in Peripheral Blood Mononuclear Cells from Atrial Fibrillation Patients.

Héctor Godoy-Marín,Hildegard Colino-Lage,José Montiel,Concepció Soler,Kenneth A Jacobson,Romain Duroux,Leif Hove-Madsen,Francisco Ciruela,Veronica Jiménez-Sábado

doi:10.3390/ijms22073467

Abstract

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia seen in clinical practice. While some clinical parameters may predict the transition from paroxysmal to persistent AF, the molecular mechanisms behind the AF perpetuation are poorly understood. Thus, oxidative stress, calcium overload and inflammation, among others, are believed to be involved in AF-induced atrial remodelling. Interestingly, adenosine and its receptors have also been related to AF development and perpetuation. Here, we investigated the expression of adenosine A2A receptor (A2AR) both in right atrium biopsies and peripheral blood mononuclear cells (PBMCs) from non-dilated sinus rhythm (ndSR), dilated sinus rhythm (dSR) and AF patients. In addition, plasma adenosine content and adenosine deaminase (ADA) activity in these subjects were also determined. Our results revealed increased A2AR expression in the right atrium from AF patients, as previously described. Interestingly, increased levels of adenosine content and reduced ADA activity in plasma from AF patients were detected. An increase was observed when A2AR expression was assessed in PBMCs from AF subjects. Importantly, a positive correlation (p = 0.001) between A2AR expression in the right atrium and PBMCs was observed. Overall, these results highlight the importance of the A2AR in AF and suggest that the evaluation of this receptor in PBMCs may be potentially be useful in monitoring disease severity and the efficacy of pharmacological treatments in AF patients.

Highlights

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, which is currently thought to affect approximately 2% of the world population
We confirmed a significant increase of A2A R density (p < 0.0001) in the right atrium from AF patients when compared to non-AF subjects (Figure 1A,B)
RsRs play a key rolerole in coronary flowflow and force generation, they have have been associated with some cardiopathological conditions, such as the genesis of been associated with some cardiopathological conditions, such as the genesis of ararrhythmias

Summary

Introduction

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, which is currently thought to affect approximately 2% of the world population. Its prevalence increases with age, affecting around 0.14% of people under 49 years old and increasing to 10-17% in people aged 80 or older [1]. This arrhythmia is known to cause an irregular and often abnormal fast heart rate and increases the risk of stroke, heart failure and other 4.0/). AF episodes typically occur when arrhythmogenic substrates, such as fibrosis and inflammation coincide [4]. Inflammation has been associated with AF-pathological processes, as well as oxidative stress or thrombogenesis [5]. It has been shown that the prevalence and prognosis of AF are highly associated with plasma levels of inflammatory biomarkers

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Results

Conclusion