Marine Gaudry1, Marion Marlinge2, Pierre Deharo3, Donato Vairo4, Sarrah Bottone5, Giovanna Mottola2, Nathalie Kipson4, Christine Criado4, Patrick Mace6, Mohamed Chefrour6, Medhy Benchaabane6, Celia Magan6, Noemi Gentil6, Thomas Cuisset7, Philippe Piquet1, David Lagier8, Emmanuel Fenouillet4, Régis Guieu9, Franck Paganelli10, Jean Ruf4. 1. Department of Vascular Surgery, Timone University Hospital, Marseille, France. 2. Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France; Laboratory of Biochemistry, Timone University Hospital, Marseille, France. 3. Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France; Department of Cardiology, Timone University Hospital, Marseille, France. 4. Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France. 5. Universtity Frederic II, Naples, Italy. 6. Laboratory of Biochemistry, Timone University Hospital, Marseille, France. 7. Department of Cardiology, Timone University Hospital, Marseille, France. 8. Laboratory of Biochemistry, Timone University Hospital, Marseille, France; Department of Anesthesia, Timone University Hospital, Marseille, France. 9. Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France; Laboratory of Biochemistry, Timone University Hospital, Marseille, France. Electronic address: guieu.regis@orange.fr. 10. Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France; Department of Cardiology, North Hospital, Marseille, France.
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 A2A receptor (A2AR). We evaluated A2AR 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 A2AR was studied, using a A2AR monoclonal antibody with agonist properties, allowing determination of A2AR affinity (KD) and cAMP production (ie.EC50). RESULTS: A2AR 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 A2AR 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 KD/EC50 ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia. CONCLUSION: A2AR expression in the arteries of patients, correlated with their expression in PBMCs. A2AR expression was lower in patients than in controls. A single blood sample (for measurement of A2AR 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.
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 A2A receptor (A2AR). We evaluated A2AR 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 A2AR was studied, using a A2AR monoclonal antibody with agonist properties, allowing determination of A2AR affinity (KD) and cAMP production (ie.EC50). RESULTS:A2AR 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 A2AR 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 KD/EC50 ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia. CONCLUSION:A2AR expression in the arteries of patients, correlated with their expression in PBMCs. A2AR expression was lower in patients than in controls. A single blood sample (for measurement of A2AR 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.