RIP140 triggers foam-cell formation by repressing ABCA1/G1 expression and cholesterol efflux via liver X receptor

FEBS Lett. 2015 Feb 13;589(4):455-60. doi: 10.1016/j.febslet.2015.01.001. Epub 2015 Jan 20.

Abstract

Receptor-interacting protein 140 (RIP140) is a multifunctional coregulator of lipid metabolism and inflammation. However, the potential role of RIP140 in atherosclerosis remains unknown. The present study investigated the impact of RIP140 on foam cell formation, a critical step in pathogenesis of atherosclerosis. The expression of RIP140 was increased in foam cells. RIP140 overexpression resulted in decreased cholesterol efflux in macrophages and their concomitant differentiation into foam cells. Moreover, RIP140 negatively regulated the macrophage expression of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), by suppressing the expression and activity of liver X receptor (LXR). These findings shed light onto the contribution of RIP140 to the development and progression of atherosclerosis, and suggest a novel therapeutic target for the treatment of atherosclerosis.

Keywords: ATP-binding cassette transporters A1 and G1; Atherosclerosis; Cholesterol efflux; Receptor-interacting protein 140.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism*
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Adaptor Proteins, Signal Transducing / physiology*
  • Cell Line
  • Cholesterol / metabolism*
  • Foam Cells / physiology*
  • Gene Expression
  • Gene Silencing
  • Humans
  • Lipoproteins, LDL / physiology
  • Liver X Receptors
  • Nuclear Proteins / physiology*
  • Nuclear Receptor Interacting Protein 1
  • Orphan Nuclear Receptors / metabolism*

Substances

  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Adaptor Proteins, Signal Transducing
  • Lipoproteins, LDL
  • Liver X Receptors
  • NRIP1 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Interacting Protein 1
  • Orphan Nuclear Receptors
  • oxidized low density lipoprotein
  • Cholesterol