Figure 2.

Insufficient omega-3/omega-6 levels promote inflammation during atherosclerosis in contrast to eicosanoid homeostasis. When the balance of lipid precursors favors more arachidonic acid (AA) than eicosapentaenoic acid (EPA), there is an insufficient production of pro-resolving eicosanoids. The inflammatory process continues unabated, leading to atherosclerosis. By contrast, when there are adequate levels of both omega-6 fatty acids (especially AA) and omega-3 fatty acids (especially EPA), the inflammatory process initiates and resolves with the temporal production of oxylipins from both omega-6 and omega-3 fatty acids. Pro-inflammatory prostaglandins such as prostaglandin E2 and leukotriene B4 from AA recruit polymorphonuclear leukocytes to extravasate through the endothelium and into the intima to initially clear inflammatory debris. This process yields with the switch in lipid mediators from pro-inflammatory to pro-resolving, which includes the production of lipoxin A4 from AA and resolvins from EPA, docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), all of which halt polymorphonuclear neutrophil (PMN) infiltration and promote efferocytosis by macrophages. ALA indicates α-linolenic acid; DGLA, dihomo-γ-linolenic acid; and LA, linoleic acid.