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

Cardiovasc Res. 2021 Apr 23;117(5):1284-1294. doi: 10.1093/cvr/cvaa275.

Abstract

Adenosine is an endogenous nucleoside that plays a major role in the physiology and physiopathology of the coronary artery system, mainly by activating its A2A receptors (A2AR). 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 A2AR improves coronary blood circulation and leads to anti-inflammatory effects, down-regulation of A2AR has many deleterious effects during CAD. A decrease in the level and/or activity of A2AR 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 fact, inducible ischaemia in CAD patients, as assessed by exercise stress test or fractional flow reserve, is associated with the presence of a reserve of A2AR 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 A2AR, based upon a new concept allowing for a new and non-invasive CAD management.

Keywords: Adenosine; Adenosine receptors; Coronary artery disease; Ischaemia; Spare receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine / metabolism*
  • Animals
  • Blood Platelets / metabolism
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / pathology
  • Coronary Circulation
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology
  • Humans
  • Plaque, Atherosclerotic
  • Purinergic Agents / therapeutic use
  • Receptor, Adenosine A2A / metabolism*
  • Signal Transduction

Substances

  • Purinergic Agents
  • Receptor, Adenosine A2A
  • Adenosine