Subcutaneous administration of casein attenuates atherosclerotic progression in male apoE(‐/‐) mice fed with high‐fat diet

The impact of casein on atherosclerotic lesion progression remains controversial. In this study, we tested the effect of casein on atherosclerotic development and its potential mechanisms in male apolipoprotein E knockout (apoE(‐/‐)) mice fed with high‐fat diet (HFD). Male apoE(‐/‐) mice fed with HFD were randomized into HFD group (subcutaneous injection with 0.5 ml of 0.9% sodium chloride daily, n = 6) and HFD + Casein group (subcutaneous injection with 0.5 ml of 10% casein daily, n = 6). Body weight was recorded at baseline and once a week thereafter. After 12 weeks of treatment, plasma lipid and inflammatory markers, and histological characterization of atherosclerotic plaques in the aortic arch and aortic sinus were analyzed. There was no significant difference in weight gain between the two groups after 12 weeks of treatment. Plasma levels of total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) were significantly lower, while high‐density lipoprotein cholesterol (HDL‐C) level tended to be higher in the HFD + Casein group compared with the HFD group. The positive percentages of atherosclerotic lesions in aortic arch and aortic sinus as well as collagen deposition in aortic sinus plaques were significantly lower in the HFD + Casein group compared with the HFD group. Plasma levels of interleukin (IL)‐1β and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were also significantly lower in the HFD + Casein group compared with the HFD group. In conclusion, subcutaneous administration of casein attenuates atherosclerotic lesion progression, possibly through decreasing fibrosis and inflammatory responses in male apoE(‐/‐) mice fed with HFD.