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Therefore, we investigated whether the n\u20103 PUFA, EPA and DHA, modulate modified low\u2010density lipoprotein (LDL) uptake by human macrophages. The uptake of fluorophore labeled acetylated LDL (AcLDL) and\/or oxidized LDL (OxLDL) by THP\u20101 macrophages and primary human monocyte\u2010derived macrophages were measured by flow cytometry following co\u2010incubation with EPA or DHA in vitro. DHA inhibited both AcLDL and OxLDL uptake in human macrophages whilst EPA reduced AcLDL and increased OxLDL uptake. These effects were only partly explained by changes in the mRNA and protein expression of key scavenger receptors, such as CD36 and scavenger receptor\u2010A, in these cells suggesting the involvement of a scavenger receptor\u2010independent mechanism. EPA and DHA inhibited macropinocytosis, as measured by Lucifer Yellow uptake, in human macrophages and attenuated the expression of Syndecan\u20104, which has been implicated in the uptake of other modified forms of LDL. EPA and DHA reduced modified LDL uptake by human macrophages through a mechanism that is in part scavenger receptor\u2010independent and may involve inhibition of macropinocytosis and Syndecan\u20104 expression. This suggests that both EPA and DHA are capable of regulating macrophage foam cell formation and adds to the evidence describing an atheroprotective role for n\u20103 PUFA, implicating them as potential therapeutic agents for the treatment of clinical atherosclerosis.<\/jats:p>","DOI":"10.1007\/s11745-011-3598-1","type":"journal-article","created":{"date-parts":[[2011,8,6]],"date-time":"2011-08-06T03:23:26Z","timestamp":1312601006000},"page":"1053-1061","source":"Crossref","is-referenced-by-count":30,"title":["Eicosapentaenoic Acid and Docosahexaenoic Acid Regulate Modified LDL Uptake and Macropinocytosis in Human Macrophages"],"prefix":"10.1002","volume":"46","author":[{"given":"James E.","family":"McLaren","sequence":"first","affiliation":[{"name":"Cardiff School of Biosciences, Cardiff University Museum Avenue Cardiff CF10 3AX UK"},{"name":"Department of Infection, Immunity and Biochemistry, Henry Wellcome Research Institute Cardiff University Heath Park Cardiff CF14 4XN 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