Suboptimal dietary zinc intake promotes vascular inflammation and atherogenesis in a mouse model of atherosclerosis

Scope Cardiovascular health is strongly influenced by diet. Zinc has antioxidant and anti‐inflammatory properties but its long‐term influence on vascular health at dietary intake levels relevant to the human population in developed countries has not been studied. We investigated the influence of suboptimal zinc intake in a Western‐type diet on the development of vascular inflammation and arterial plaque in apoE knock‐out ( AEKO ) mice. Methods and results Weanling AEKO and wild‐type ( WT ) controls were given high saturated fat (21% w/w) and high cholesterol (0.15%) semi‐synthetic diets containing 3 or 35 mg Zn/kg ( AEKO and WT ) or 8 mg Zn/kg ( AEKO only) for over 6 months. AEKO mice on zinc intakes of 3 and 8 mg Zn/kg (suboptimal zinc) developed significantly ( p < 0.05) more aortic plaque than AEKO mice consuming 35 mg Zn/kg (adequate zinc). Circulating levels of interleukin‐1β, interleukin‐6 and soluble vascular adhesion molecule‐1 were significantly ( p < 0.05) raised at the lowest zinc intake in AEKO mice, as compared to zinc‐adequate controls. Plasma total cholesterol and total protein were also significantly ( p < 0.05) increased at the lowest zinc intake. Conclusion We propose that suboptimal dietary zinc intake raises circulating pro‐atherogenic lipoprotein levels that promote vascular inflammation and enhance arterial plaque formation.