The atheroprotective role of fucoidan involves the reduction of foam cell formation by altering cholesterol flux-associated factors in macrophages

Atherosclerosis is characterized by the accumulation of lipid-laden cells in the arterial walls, resulting from dysregulation of cholesterol homeostasis in the macrophage, triggered by oxidized low-density lipoprotein (oxLDL). Previous studies have shown that fucoidan, a sulfated polysaccharide from brown seaweeds, has several atheroprotective activities, however, the mechanism of fucoidan protection is not fully understood. Thus, we investigated the effect of fucoidan on atherogenesis in apolipoprotein E-deficient (ApoE−/−) mice, on oxLDL uptake by macrophages, and on the expression of the flux-associated scavenger receptors by macrophages. Also, we examined the absorption and biodistribution of orally administered fucoidan. ApoE−/− mice fed on a cholesterol-rich diet supplemented with 1% fucoidan showed reduced dyslipidemia and atherosclerosis. Fucoidan was detected in blood and peripheral tissue after gavage, suggesting that it can exert direct systemic effects. In vitro, fucoidan reduced macrophage oxLDL uptake, which resulted in lower foam cell formation. This effect was associated with downregulation of the cholesterol influx-associated scavenger receptor (SR)-A expression, and upregulation of the cholesterol efflux-associated SR-B1 expression. In conclusion, fucoidan prevented oxLDL-mediated foam cell formation in macrophages by downregulating SR-A1/2 and by up-regulating SR-B1. [Display omitted] •Fucoidan is absorbed across the intestinal tract and reaches diverse tissues.•Fucoidan reduces lipid accumulation and peroxidation in the liver.•Fucoidan attenuated dyslipidemia and atherosclerosis in ApoE−/− mice.•Fucoidan reduced the oxLDL uptake and macrophage-derived foam cells formation.•Fucoidan reduced SR-A1/2 (influx) expression and increased SR-B1 (efflux) expression.