Recent advances in the role of the adenosinergic system in coronary artery disease

Adenosine is an endogenous nucleoside that plays a major role in the physiology and physiopathology of the coronary artery system, mainly by activating its A(2A) receptors (A(2A)R). Adenosine is released by myocardial, endothelial, and immune cells during hypoxia, ischaemia, or inflammation, each condition being present in coronary artery disease (CAD). While activation of A(2A)R( ) improves coronary blood circulation and leads to anti-inflammatory effects, down-regulation of A(2A)R has many deleterious effects during CAD. A decrease in the level and/or activity of A(2A)R leads to: (i) lack of vasodilation, which decreases blood flow, leading to a decrease in myocardial oxygenation and tissue hypoxia; (ii) an increase in the immune response, favouring inflammation; and (iii) platelet aggregation, which therefore participates, in part, in the formation of a fibrin-platelet thrombus after the rupture or erosion of the plaque, leading to the occurrence of acute coronary syndrome. Inflammation contributes to the development of atherosclerosis, leading to myocardial ischaemia, which in turn leads to tissue hypoxia. Therefore, a vicious circle is created that maintains and aggravates CAD. In some cases, studying the adenosinergic profile can help assess the severity of CAD. In act, inducible ischaemia in CAD patients, as assessed by exercise stress test or fractional flow reserve, is associated with the presence of a reserve of A(2A)R called spare receptors. The purpose of this review is to present emerging experimental evidence supporting the existence of this adaptive adenosinergic response to ischaemia or inflammation in CAD. We believe that we have achieved a breakthrough in the understanding and modelling of spare A(2A)R, based upon a new concept allowing for a new and non-invasive CAD management. [GRAPHICS] .

Automated summary

Adenosine, through its A(2A) receptors, plays a crucial role in the coronary artery system by regulating blood circulation and inflammation. Down-regulation of A(2A) receptors in CAD can lead to adverse effects such as reduced vasodilation, increased immune response, and platelet aggregation, contributing to the progression and severity of the disease.