title: Lowbush blueberries inhibit scavenger receptors CD36 and SR-A expression and attenuate foam cell formation in ApoE-deficient mice.
abstract: Blueberries have recently been reported to reduce atherosclerotic lesion progression in apoE deficient (apoE(-/-)) mice. However, the underlying mechanisms are not fully understood. The objective of this study was to determine whether lowbush blueberries altered scavenger receptor expression and foam cell formation in apoE(-/-) mice. ApoE(-/-) mice were fed AIN-93 diet (CD) or CD formulated to contain 1% freeze-dried lowbush blueberries (BB) for 20 weeks. Gene expression and protein levels of scavenger receptor CD36 and SR-A in aorta and thioglycollate-elicited peritoneal macrophages (PM) were lower in mice fed BB (P < 0.05). In the second experiment, apoE(-/-) mice were fed CD or BB for 5 weeks. PM were collected and cultured. Gene expression and protein levels of CD36 and SR-A were found to be lower in PM of BB fed mice (P < 0.05). In PM from BB fed mice, fewer oxLDL-induced foam cells were formed compared to those from mice fed CD. Gene expression and protein levels of PPARγ were lower in the PM of BB fed mice (P < 0.05). Detectable isomers of hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acid (HETEs) were also lower in the PM of BB fed mice (P < 0.05 or P < 0.01). In conclusion, BB inhibited expression of the two major scavenger receptors CD36 and SR-A in PM of apoE(-/-) mice, at least in part through down-regulating PPARγ and reducing its endogenous ligands HODEs and HETEs. We proposed that BB mediated reduction of scavenger receptor expression and attenuation of oxLDL-induced foam cell formation in PM of apoE(-/-) mice are important mechanisms of the athero-protective effects of BB.
authors.affiliation: USDA Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Xie
authors.forename: Jie
authors.initials: J
authors.lastname: Kang
authors.forename: Jin-Ran
authors.initials: JR
authors.lastname: Chen
authors.forename: Oxana P
authors.initials: OP
authors.lastname: Lazarenko
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Ferguson
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Nagarajan
authors.forename: Xianli
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D029798:Blueberry Plants / Q000737:chemistry*; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005487:Foam Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D028321:Plant Preparations / Q000008:administration & dosage*; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D047495:PPAR gamma; D028321:Plant Preparations; D051117:Scavenger Receptors, Class A