Diets rich in ω-6 polyunsaturated fatty acids, of which arachidonic acid is an example, have been associated with low levels of LDL cholesterol and a high ratio of HDL cholesterol levels to total cholesterol levels in plasma, which are factors thought to be atheroprotective. Demetz et al. mined data from genome-wide association studies involving >100,000 individuals of European ancestry to identify common variants in genes involved in the metabolism of arachidonic acid that associate with altered plasma lipid levels. They validated the results in mice by pharmacological modulation of arachidonic acid metabolism with aspirin, which stimulated the generation of leukotrienes and lipoxins in the liver and resulted in increased reverse cholesterol transport. Treatment of mice with lipoxin mimetics effectively decreased plasma levels of LDL cholesterol. The results highlight the arachidonic acid metabolic pathway as a possible therapeutic avenue for treating atherosclerosis.