Homocysteine concentration and adenosine A_2A receptor production by peripheral blood mononuclear cells in coronary artery disease patients.

ABSTRACT: 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.

SUBMITTER: Deharo P 

PROVIDER: S-EPMC7417719 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature