Homocysteine concentration and adenosine A2A receptor production by peripheral blood mononuclear cells in coronary artery disease patients

摘要

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 Asub2A/sub receptors (Asub2A/subR). We addressed in CAD patients the relationship between HCy and Asub2A/subR production, and in cellulo the effect of HCy on Asub2A/subR function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated Asub2A/subR production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on Asub2A/sub R production as well as on basal and stimulated cAMP production following Asub2A/sub 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). Asub2A/sub 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 Asub2A/sub R production ( r =??0.43; P ?0.0001), with decreased Asub2A/sub R production above 25?μM HCy. In cellulo, HCy inhibited Asub2A/subR production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with Asub2A/sub R production in CAD patients, as well as with Asub2A/sub R and cAMP production in cellulo. The decrease in Asub2A/sub R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.