title: [The in vitro anti-atherosclerotic activity of compound E0869].
abstract: ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators for treating atherosclerosis by using cell-based high throughput screening models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1-oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit. The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were 160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1-LUC HepG2 cell were 3.79 and 1.42 pμol- x ,(-1) respectively. E0869 could upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam cell assay showed that E0869 could inhibit lipids accumulation in mouse peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7. In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good anti-atherosclerotic activity in vitro.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Xu
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Si
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy*; D001692:Biological Transport; D002784:Cholesterol; D056945:Hep G2 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D012333:RNA, Messenger; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D012333:RNA, Messenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol