Abstract
Monounsaturated fat (MUF)-rich Mediterranean-type diet (MedD) has been reported to improve atherosclerotic outcome in clinical studies, but the underlying mechanism is ill defined. Circulating foamy monocytes (FMs, monocytes with intracellular lipid droplets), which are CD11c + and highly adherent to inflamed endothelium, contribute to atherosclerosis development. In the present study, we investigated the influence of MedD on FM formation and its contribution to atherosclerosis in mice. LDLR -/- mice were fed MedD with high cholesterol (MedD [w/w, 21% total fat from olive oil and nut] containing 2.6% saturated fat and 13.4% MUF; 0.2% cholesterol) or western diet (WD, 21% milkfat-containing 13.3% saturated fat and 5.9% MUF; 0.2% cholesterol), with normal diet (ND) as control. Lesion area of the whole aorta examined by oil red staining at 3 months was significantly reduced in mice on MedD, compared to WD. Although plasma triglyceride levels were lower in mice on MedD than on WD, the free fatty acid profile indicated that MUFs concentration in plasma significantly increased in mice on MedD. Further, FMs from mice on MedD circulated at lower proportions and exhibited lower side scatter (SSC) than WD, indicating less lipid accumulation. Lipid accumulation in FMs from mice on WD accelerated their conversion from CD11c - /CD36 + to CD11c + /CD36 + compared to mice on ND. In contrast, this accelerated conversion did not occur in mice on MedD. Compared to WD, MedD reduced the number of firmly arrested CD11c + monocytes on vascular cell adhesion molecule-1 and E-selectin coated coverslips detected in an ex-vivo shear flow assay. Similarly, fewer CD11c + macrophages were observed in the lesion of aortic sinus in mice on MedD than on WD. In summary, compared to WD high in saturated fat and cholesterol, MedD high in MUF and cholesterol lowered triglyceride levels, inhibited foamy monocyte formation and adhesion, and reduced atherosclerosis in LDLR -/- mice.
Published Version
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