Homocysteine concentration and adenosine A(2A) receptor production by peripheral blood mononuclear cells in coronary artery disease patients

Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A(2A) receptors (A(2A)R). We addressed in CAD patients the relationship between HCy and A(2A)R production, and in cellulo the effect of HCy on A(2A)R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A(2A)R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A(2A) R production as well as on basal and stimulated cAMP production following A(2A) R activation by an agonist‐like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7‐45] vs 8 [5‐12] µM, P < 0.001). A(2A) R production was lower in patients vs controls (1.1[0.62‐1.6] vs 1.53[0.7‐1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A(2A) R production (r = −0.43; P < 0.0001), with decreased A(2A) R production above 25 µM HCy. In cellulo, HCy inhibited A(2A)R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A(2A) R production in CAD patients, as well as with A(2A) R and cAMP production in cellulo. The decrease in A(2A) R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.