Effect of Extra Virgin Olive Oil High in Bioactive Compounds on Atherosclerosis in Apoe‐Deficient Mice

To test the effects of extra virgin olive oil (EVOO) enriched in specific bioactive compounds (EVOO HBC) on atherosclerosis and fatty liver, three isocaloric Western diets differing in the type of fat (palm, EVOO, or EVOO HBC) were fed to Apoe‐deficient mice for 12 weeks. Plasma lipids, lipoprotein characterization, circulating CD36‐expressing monocytes, and M2 peritoneal macrophages were quantified. Hepatic squalene and cross‐sectional and en face atherosclerotic lesions were analyzed. Compared to the palm group, plasma triglyceride and glucose levels increased, while APOA1, paraoxonase 1 activity, and lipoprotein oxidation decreased in mice fed both EVOO groups. The latter stored liver squalene according to the amount consumed. En face and cross‐sectional atherosclerotic lesions were lower in the EVOO groups. CD36 expression in circulating monocytes was lower and M2 peritoneal macrophages were higher in the EVOO groups. In males, there was a reduced presence of CD68‐expressing cells in atherosclerotic plaques, while in females, there was a reduction in en face lesions that negatively correlated with high‐density lipoprotein (HDL)‐phospholipid efflux. The recruitment of macrophages into atherosclerotic plaques and the improvement of HDL efflux may be sex‐dependent and attributable to the high content of squalene and a specific oleuropein aglycone.