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

AbstractOBJECTIVE:
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-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.
AuthorsYan Wang, Jian-Feng Wu, Yan-Yan Tang, Min Zhang, Yuan Li, Kong Chen, Meng-Ya Zeng, Feng Yao, Wei Xie, Xi-Long Zheng, Gao-Feng Zeng, Chao-Ke Tang
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 452 Issue 4 Pg. 998-1003 (Oct 03 2014) ISSN: 1090-2104 [Electronic] United States
PMID25223800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • NF-kappa B
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Urotensins
  • urotensin II
  • Cholesterol
Topics
  • ATP Binding Cassette Transporter 1 (metabolism)
  • Cell Line
  • Cell Proliferation (drug effects, physiology)
  • Cholesterol (metabolism)
  • Down-Regulation (drug effects, physiology)
  • Foam Cells (cytology, drug effects, physiology)
  • Humans
  • Lipid Metabolism (drug effects, physiology)
  • MAP Kinase Signaling System (drug effects, physiology)
  • NF-kappa B (metabolism)
  • STAT3 Transcription Factor (metabolism)
  • Signal Transduction (drug effects, physiology)
  • Urotensins (pharmacology)

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