Insights into the role of the resolvin D2-GPR18 signaling axis in cardiovascular physiology and disease

Non-resolving inflammation is an underpinning of cardiovascular diseases including atherosclerosis. The resolution of inflammation is an active and highly coordinated process that involves the generation of specialized pro-resolving mediators (SPMs), and other factors including proteins, gases, and nucleotides. SPMs comprise a superfamily of lipid mediators that includes lipoxins, resolvins, maresins and protectins. SPMs act through distinct G protein-coupled receptors (GPCRs) and have been extensively studied in animal models of cardiovascular diseases. An emerging body of literature suggests that SPMs have protective roles in atherosclerosis as demonstrated using specific SPM as well as mice deficient in their receptors. This review will highlight a relatively new pro-resolving signaling axis, namely Resolvin D2-GPR18, and how understanding detailed mechanisms and cellular specificity of this signaling axis may help inform the development of more targeted pro-resolution therapies for atherosclerosis and related cardiovascular pathologies.