title: CLI-095 decreases atherosclerosis by modulating foam cell formation in apolipoprotein E-deficient mice.
abstract: Toll-like receptor 4 (TLR4) is considered to have a critical role in the occurrence and development of atherosclerosis in atherosclerosis-prone mice; however, it remains uncertain whether treatment with a TLR4 inhibitor may attenuate atherosclerosis. The present study aimed to determine the vascular protective effects of the TLR4 inhibitor CLI-095 on apolipoprotein E‑deficient (ApoE‑/‑) mice. ApoE‑/‑ mice were fed either chow or a high‑fat diet, and were treated with or without CLI‑095 for 10 weeks. The mean atherosclerotic plaque area in the aortic sections of CLI‑095‑treated mice was 54.3% smaller than in the vehicle‑treated mice (P=0.0051). In vitro, murine peritoneal macrophages were treated with or without CLI‑095, and were subsequently stimulated with oxidized low‑density lipoprotein. Treatment with CLI‑095 markedly reduced the expression levels of lectin‑like oxidized low‑density lipoprotein receptor‑1 and acyl-coenzyme A:cholesterol acyltransferase‑1, and significantly upregulated the expression levels of ATP‑binding cassette transporter A1, predominantly via suppressing activation of the TLR4/nuclear factor‑κB signaling pathway. The results of the present study indicated that the TLR4 inhibitor CLI‑095 has the ability to suppress the progression of atherosclerosis in an in vivo model by reducing macrophage foam cell formation.
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Wan
authors.affiliation: Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Xian-Jing
authors.initials: XJ
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D004195:Disease Models, Animal; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D002785:Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D015415:Biomarkers; D008055:Lipids; D013449:Sulfonamides; D051197:Toll-Like Receptor 4; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1