Pharmacological profile of adenosine A 2A receptors in patients with lower extremity peripheral artery disease and associated coronary artery disease: A pilot study

• Published in: International journal of cardiology Vol. 285; p. 121
• Main Authors: Gaudry, Marine, Marlinge, Marion, Deharo, Pierre, Vairo, Donato, Bottone, Sarrah, Mottola, Giovanna, Kipson, Nathalie, Criado, Christine, Mace, Patrick, Chefrour, Mohamed, Benchaabane, Medhy, Magan, Celia, Gentil, Noemi, Cuisset, Thomas, Piquet, Philippe, Lagier, David, Fenouillet, Emmanuel, Guieu, Régis, Paganelli, Franck, Ruf, Jean
• Format: Journal Article
• Language: English
• Published: Netherlands 15.06.2019
• Subjects: Adenosine - pharmacology; Aged; Biomarkers - metabolism; Coronary Artery Disease - drug therapy; Coronary Artery Disease - etiology; Coronary Artery Disease - metabolism; Female; Humans; Leukocytes, Mononuclear - metabolism; Lower Extremity - blood supply; Male; Peripheral Arterial Disease - complications; Peripheral Arterial Disease - drug therapy; Peripheral Arterial Disease - metabolism; Pilot Projects; Prognosis; Receptor, Adenosine A2A - metabolism; Vasodilator Agents - pharmacology
• ISSN: 1874-1754
• DOI: 10.1016/j.ijcard.2019.02.055

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 receptor (A R). We evaluated A R expression and function in peripheral blood mononuclear cells (PBMCs) and the femoral artery tissues of patients with LE-PAD. 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 R was studied, using a A R monoclonal antibody with agonist properties, allowing determination of A R affinity (K ) and cAMP production (ie.EC ). A R 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 R 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/10 cells (P < 0.05) and 375 [160-659] vs 670 [410-980] pg/10 cells (P < 0.05), respectively. A high K /EC ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia. A R expression in the arteries of patients, correlated with their expression in PBMCs. A R expression was lower in patients than in controls. A single blood sample (for measurement of A R 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.