Figure 7.

Model of atherosclerosis as a nonresolving form of vascular inflammation. The essential ω-6 PUFA arachidonic acid (AA) is released from phospholipids in cells by the action of cytosolic phospholipase A2. After specific enzymatic steps, AA is converted into different families of mediators: prostaglandins (PGs) and leukotrienes (LTs), which are mostly proinflammatory molecules, and lipoxins such as LXA4, a stop-inflammation mediator. The essential ω-3 PUFA DHA is converted to two novel mediators, RvD1 and PD1, that promote resolution. We propose a model in which absence of macrophage 12/15LO leads to a deficiency in proresolving end products, RvD1 and PD1, as well as LXA4, locally at the site of the ongoing inflammation, crippling multiple proresolving functions, leaving the proinflammatory milieu unabated, and fueling atherosclerosis progression. LOX, lipoxygenase.