title: Quercetin increases macrophage cholesterol efflux to inhibit foam cell formation through activating PPARγ-ABCA1 pathway.
abstract: The accumulation of cholesterol in macrophages could induce the formation of foam cells and increase the risk of developing atherosclerosis. We wonder if quercetin, one of flavonoids with anti-inflammation functions in different cell types, could elevate the development of foam cells formation in atherosclerosis. We treated foam cells derived from oxLDL induced THP-1 cells with quercetin, and evaluated the foam cells formation, cholesterol content and apoptosis of the cells. We found that quercetin induced the expression of ABCA1 in differentiated THP-1 cells, and increased the cholesterol efflux from THP-1 cell derived foam cells. Eventually, cholesterol level and the formation of foam cell derived from THP-1 cells decreased after quercetin treatment. In addition, quercetin activated PPARγ-LXRα pathway to upregulate ABCA1 expression through increasing protein level of PPARγ and its transcriptional activity. Inhibition of PPARγ activity by siRNA knockdown or the addition of chemical inhibitor, GW9662, abolished quercetin induced ABCA1 expression and cholesterol efflux in THP-1 derived macrophages. Our data demonstrated that quercetin increased cholesterol efflux from macrophages through upregulating the expressions of PPARγ and ABCA1. Taken together, increasing uptake of quercetin or quercetin-rich foods would be an effective way to lower the risk of atherosclerosis.
authors.affiliation: Department of Cardiovascular Internal Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China ; Department of Cardiovascular Internal Medicine, The Second Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiovascular Internal Medicine, The Second Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China.
authors.forename: En
authors.initials: E
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gerontology, The Second Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Ultrasonography, The Second Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Cardiovascular Internal Medicine, The Second Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Niu
authors.affiliation: Department of Cardiovascular Internal Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou, P. R. China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Qiu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C457499:2-chloro-5-nitrobenzanilide; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000813:Anilides; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D011794:Quercetin
keywords: ABCA1; PPARγ; Quercetin; atherosclerosis; foam cells