Interleukin-17 deficiency reduced vascular inflammation and development of atherosclerosis in Western diet-induced apoE-deficient mice

ObjectiveSeveral reports describe the role of interleukin (IL)-17 in the development of atherosclerosis; however, its precise role remains controversial. We generated double-deficient mice for apolipoprotein E (apoE) and IL-17 (apoE−/−IL-17−/− mice) and investigated the effect of IL-17 deficiency on vascular inflammation and atherosclerosis.Methods and resultsAtherosclerotic plaque areas in apoE−/−IL-17−/− mice fed a Western diet (WD) were significantly reduced compared with those in apoE−/− mice. No significant differences in plasma lipid profiles were observed between apoE−/− and apoE−/−IL-17−/− mice. The number of infiltrated macrophages in the plaques was significantly decreased in WD-fed apoE−/−IL-17−/− mice compared with WD-fed apoE−/− mice, whereas vascular smooth muscle cell content was not altered by IL-17 deficiency. Expression of inflammatory cytokines (MCP-1, IL-1β, IL-6, IFN-γ, and IL-12 p40) and scavenger receptors (Msr-1, Scarb1, and Olr1) in the plaques was inhibited in WD-fed apoE−/−IL-17−/− mice. Furthermore, expression of inducible nitric oxide (M1 marker) and arginase-1 (M2 marker) was inhibited in WD-fed apoE−/−IL-17−/− mice.ConclusionOur results indicate that IL-17 deficiency reduces vascular inflammation and atherosclerosis and that modulation of IL-17 could be a potential target for prevention and treatment of atherosclerosis.

► IL-17 deficiency reduced atherosclerosis in Western diet-fed apoE−/− mice.
► IL-17 deficiency decreased the expression of cytokines and scavenger receptors.
► IL-17 upregulated the expression of IL-12 p40 and IL-6 in macrophages.