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

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.

A2 Adenosine Receptor Subtypes Overproduction in Atria of Perioperative Atrial Fibrillation Patients Undergoing Cardiac Surgery: A Pilot Study

“…We observed a correlation between adenosine receptor expression in PBMCs and atria regardless of the subtype considered. These data also confirmed that PBMCs are a useful model for studying the adenosinergic system of AF patients (23). Finally, we do not observe a significant correlation between BAC and LA receptor production.…”

Adenosine Receptor Reserve and Long-Term Potentiation: Unconventional Adaptive Mechanisms in Cardiovascular Diseases?

“…In addition, a higher adenosine plasma level in the left atria has been shown to be associated with AF episodes that normalize after cardioversion [ 75 ]. High A 2A R production in an AF patient’s atria was also reported [ 76 , 77 ]. In particular, an increased adenosine blood level, reduced adenosine deaminase activity, and upregulation of A 2A R of PBMC have been reported in patients with AF.…”

“…In particular, an increased adenosine blood level, reduced adenosine deaminase activity, and upregulation of A 2A R of PBMC have been reported in patients with AF. In addition, a positive and significant correlation between A 2A R production in the right atrium and in PBMC was observed [ 77 ].…”

A2A Adenosine Receptor as a Potential Biomarker and a Possible Therapeutic Target in Alzheimer’s Disease

“…An important issue that needs to be addressed concerns the specificity of this adenosine receptor subtype as a potential biomarker of AD. Regarding specificity in particular, an upregulation of them was already found in lymphocytes from ischemic stroke patients [ 112 , 113 , 114 ], amyotrophic lateral sclerosis and multiple sclerosis [ 115 , 116 ], Huntington’s and Parkinson’s disease [ 106 , 117 ], chronic heart failure and cardiac transplantation [ 105 ], and in PMBCs from atrial fibrillation patients [ 118 ]. In spite of this wide overexpression of A 2A receptors in lymphocytes and neutrophils of patients with pathologies of different nature and affecting different organs, the evidence related to their upregulation in AD has been relieved in platelets, and whether the same result is present in lymphocytes has yet to be determined.…”