Pharmacological profile of adenosine A2A receptors in patients with lower extremity peripheral artery disease and associated coronary artery disease: A pilot study

Abstract

Background: Altered blood flow occurs in patients with low extremity peripheral artery disease (LE-PAD). LE-PAD is mostly associated with coronary artery disease (CAD). Adenosine is an endogenous nucleoside that affects both coronary and limb artery blood flow, mostly via the adenosine A_2A receptor (A_2AR). We evaluated A_2AR expression and function in peripheral blood mononuclear cells (PBMCs) and the femoral artery tissues of patients with LE-PAD.

Methods: Artery tissues and PBMCs were sampled in 24 patients with intermittent claudication, and compared with PBMCs in 24 healthy subjects. Expression and function of A_2AR was studied, using a A_2AR monoclonal antibody with agonist properties, allowing determination of A_2AR affinity (K_D) and cAMP production (ie.EC₅₀).

Results: A_2AR expression on PBMCs was lower in patients than controls (median1.3 [range 0.6-1.8] vs 1.75 [1.45-2.1] arbitrary units; P < 0.01), and correlated with A_2AR expression in artery tissues (Pearson's r = 0.71; P < 0.01). Basal and maximally stimulated cAMP production of PBMCs was lower in patients vs controls: 172 [90-310] vs 244 [110-380] pg/10⁶ cells (P < 0.05) and 375 [160-659] vs 670 [410-980] pg/10⁶ cells (P < 0.05), respectively. A high K_D/EC₅₀ ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia.

Conclusion: A_2AR expression in the arteries of patients, correlated with their expression in PBMCs. A_2AR expression was lower in patients than in controls. A single blood sample (for measurement of A_2AR expression on PBMCs) may help to screen patients with LE-PAD, whereas the presence of spare receptors may help with risk stratification before vascular surgery in CAD patients with high risk of myocardial ischemia.