title: Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages.
abstract: OBJECTIVE
  Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages.
  
  
  RESULTS
  Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively.
  
  
  CONCLUSIONS
  Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China.
authors.forename: Kong
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China.
authors.forename: Meng-Ya
authors.initials: MY
authors.lastname: Zeng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China. Electronic address: qichingnudou@tom.com.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Zeng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014579:Urotensins / Q000494:pharmacology*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014579:Urotensins; C029677:urotensin II; D002784:Cholesterol
keywords: ABCA1; Cholesterol efflux; ERK; NF-κB; Urotensin II