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Title: Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages

Highlights: • U II reduces cholesterol efflux in THP-1 macrophages. • U II decreases the expression of ABCA1. • Inhibition of the ERK/NF-κB pathway reduces U II effects on ABCA1 expression and cholesterol efflux. - 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. Methods and 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. Conclusion: 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-κBmore » pathway and reducing cholesterol efflux to promote macrophage foam cell formation.« less
Authors:
 [1] ;  [2] ; ; ;  [3] ; ;  [2] ; ;  [3] ;  [4] ;  [2] ;  [3]
  1. Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan (China)
  2. Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan (China)
  3. Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang 421001, Hunan (China)
  4. 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)
Publication Date:
OSTI Identifier:
22416771
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARTERIOSCLEROSIS; ATP; CELL WALL; CHOLESTEROL; FOAMS; HUMAN POPULATIONS; INHIBITION; LIPIDS; MACROPHAGES; PATHOGENESIS; PROTEINS