The involvement of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a 12-lipooxygenase product of arachidonic acid, has been suggested in atherosclerosis. However, its effect on macrophage functions is not completely understood, so far. The uptake of apoptotic cells (efferocytosis) by macrophages is an anti-inflammatory process, impaired in advanced atherosclerotic lesions. This process induces the release of the anti-inflammatory cytokine interleukin-10 (IL-10), and it is regulated by Rho-GTPases, whose activation involves the isoprenylation, a modification inhibited by statins. We assessed 12-HETE levels in serum of coronary artery disease (CAD) patients, and explored 12(S)-HETE in vitro effect on monocyte-derived macrophage (MDM) efferocytosis.
Manega CM, Fiorelli S, Porro B, Turnu L, Cavalca V, Bonomi A, Cosentino N, Di Minno A, Marenzi G, Tremoli E, Eligini S. 12(S)-Hydroxyeicosatetraenoic acid downregulates monocyte-derived-macrophage efferocytosis: new insights in atherosclerosis. Pharmacol Res 2019 Apr 24. pii: S1043-6618(18)31592-5. doi: 10.1016/j.phrs.2019.03.012.