title: Spare Adenosine A2a Receptors Are Associated With Positive Exercise Stress Test In Coronary Artery Disease.
abstract: During exercise, cardiac oxygen-consumption increases and the resulting low oxygen level in myocardium triggers coronary vasodilation. This response to hypoxia is controlled notably by the vasodilator adenosine and its A2Areceptor (A2AR). According to the "spare receptor" pharmacological model, a strong A2AR-mediated response can occur in the context of a large number of receptors remaining unoccupied, activation of only a weak fraction of A2AR (evaluated using KD) resulting in maximal cAMP production (evaluated using EC50), and hence in maximal coronary vasodilation. In coronary artery disease (CAD), myocardial ischemia limits adaptation to exercise, which is commonly detected using the exercise stress test (EST). We hypothesized that spare A2AR are present in CAD patients to correct ischemia. Seventeen patients with angiographically-documented CAD and 17 control subjects were studied. We addressed adenosine-plasma concentration and A2AR-expression at the mononuclear cell-surface, which reflects cardiovascular expression. The presence of spare A2AR was tested using an innovative pharmacological approach based on a homemade monoclonal antibody with agonist properties. EST was positive in 82% of patients, and in none of the controls. Adenosine plasma-concentration increased by 60% at peak exercise in patients only (p<0.01). Most patients (65%), and none of the controls, had spare A2AR (identified when EC50/KD≤0.1) and a low A2AR-expression (mean: -37% vs controls; p<0.01). All patients with spare A2AR had a positive EST whereas the subjects without spare A2AR had a negative EST (p<0.05). Spare A2AR are therefore associated with positive EST in CAD patients and their detection may be used as a diagnostic marker.
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille.|INSERM, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Ruf
authors.affiliation: Department of Cardiology, Nord Hospital, Marseille, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
authors.affiliation: Department of Cardiology, Nord Hospital, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kipson
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mottola
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.|Laboratory of Biochemistry, Timone Hospital, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Fromonot
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Condo
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Boussuges
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Bruzzese
authors.affiliation: Department of Intensive Care, Timone Hospital, Marseille, France.
authors.forename: Françis
authors.initials: F
authors.lastname: Kerbaul
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Jammes
authors.affiliation: Department of Cardiac Surgery, Timone Hospital, Marseille, France.
authors.forename: Vlad
authors.initials: V
authors.lastname: Gariboldi
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Franceschi
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.|Institut des Sciences Biologiques, CNRS, Marseille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Fenouillet
authors.affiliation: UMR MD2, Aix-Marseille University and Institute of Biological Research of the French Army, Marseille, France.|Department of Cardiology, Nord Hospital, Marseille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Guieu
keywords: adenosine; cardiovascular disease; coronary artery disease; ischemia; receptor