title: Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: implication in the anti-atherosclerotic mechanism of dietary flavonoids.
abstract: Epidemiological studies suggest that the consumption of flavonoid-rich diets decreases the risk of cardiovascular diseases. However, the target sites of flavonoids underlying the protective mechanism in vivo are not known. Quercetin represents antioxidative/anti-inflammatory flavonoids widely distributed in the human diet. In this study, we raised a novel monoclonal antibody 14A2 targeting the quercetin-3-glucuronide (Q3GA), a major antioxidative quercetin metabolite in human plasma, and found that the activated macrophage might be a potential target of dietary flavonoids in the aorta. Immunohistochemical studies with monoclonal antibody 14A2 demonstrated that the positive staining specifically accumulates in human atherosclerotic lesions, but not in the normal aorta, and that the intense staining was primarily associated with the macrophage-derived foam cells. In vitro experiments with murine macrophage cell lines showed that the Q3GA was significantly taken up and deconjugated into the much more active aglycone, a part of which was further converted to the methylated form, in the activated macrophages. In addition, the mRNA expression of the class A scavenger receptor and CD36, which play an important role for the formation of foam cells, was suppressed by the treatment of Q3GA. These results suggest that injured/inflamed arteries with activated macrophages are the potential targets of the metabolites of dietary quercetin. Our data provide a new insight into the bioavailability of dietary flavonoids and the mechanism for the prevention of cardiovascular diseases.
authors.affiliation: Department of Food Science, Graduate School of Nutrition and Biosciences, the University of Tokushima, Tokushima, Japan. y-kawai@nutr.med.tokushima-u.ac.jp
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Kawai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shiba
authors.forename: Satomi
authors.initials: S
authors.lastname: Saito
authors.forename: Kaeko
authors.initials: K
authors.lastname: Murota
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masaya
authors.initials: M
authors.lastname: Kanayama
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000975:Antioxidants / Q000032:analysis* / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood* / Q000473:pathology / Q000517:prevention & control; D018955:CD36 Antigens / Q000096:biosynthesis; D002417:Cattle; D002460:Cell Line; D004032:Diet; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D011794:Quercetin / Q000097:blood* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D000975:Antioxidants; D018955:CD36 Antigens; D020719:Glucuronides; D012333:RNA, Messenger; D011794:Quercetin