Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling

Abstract

Inflammation in arterial walls leads to coronary artery disease (CAD). Because specialized proresolving lipidmediators (SPMs; lipoxins, resolvins, and protectins) stimulate resolution of inflammation in animalmodels, we tested whether n-3 fatty acids impact SPM profiles in patients with CAD and promote clot remodeling. Six patients with stable CAD were randomly assigned to either treatment with daily 3.36 g Lovaza for 1 yr or without. Targeted lipid mediator-metabololipidomics showed that both groups had absence of resolvin D1 (RvD1), RvD2, RvD3, RvD5 and resolvin E1-all of which are present in healthy patients. Those not taking Lovaza had an absence of aspirin-triggered resolvin D3 (AT-RvD3) and aspirin-triggered lipoxin B4 (AT-LXB4). Lovaza treatment restored AT-RvD3 and AT-LXB4 andgave levels of RvD6 and aspirin-triggeredprotectin D1(AT-PD1) twice ashigh(resolvin E2 ∼5 fold) as well as lower prostaglandins. Principal component analysis indicated positive relationships for patients with CAD who were receiving Lovaza with increased AT-RvD3, RvD6, AT-PD1, and AT-LXB4. SPMs identified in Lovaza-treated patients with CAD enhanced ∼50% at 1 nM macrophage uptake of blood clots. These results indicate that patients with CAD have lower levels and/or absence of specific SPMs that were restored with Lovaza; these SPMs promote macrophage phagocytosis of blood clots. Together, they suggest that low vascular SPMs may enable progression of chronic vascular inflammation predisposing to coronary atherosclerosis and to thrombosis.