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

Int J Mol Sci. 2021 Mar 27;22(7):3467. 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.

Keywords: adenosine; adenosine A2A receptor; adenosine deaminase; atrial fibrillation; peripheral blood mononuclear cells.

MeSH terms

  • Adenosine / metabolism
  • Adenosine Deaminase / metabolism
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / blood*
  • Atrial Remodeling
  • Female
  • HEK293 Cells
  • Heart Atria
  • Humans
  • Leukocytes, Mononuclear / cytology*
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Receptor, Adenosine A2A / blood*
  • Up-Regulation*

Substances

  • ADORA2A protein, human
  • Receptor, Adenosine A2A
  • Adenosine Deaminase
  • Adenosine