Format

Send to

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):637-43. Epub 2004 Jan 29.

The "CholesteROR" protective pathway in the vascular system.

Author information

  • 1Laboratoire Développement et Vieillissement du Système Nerveux, Université P. & M. Curie-CNRS, UMR NPA 7102, case 14, 9 quai Saint Bernard, 75005 Paris, France.

Abstract

Retinoic acid receptor-related Orphan Receptor alpha (RORalpha) is a member of the nuclear hormone receptor superfamily. RORalpha has long been considered as a constitutive activator of transcription in the absence of exogenous ligand; however, cholesterol has recently been identified as a natural ligand of RORalpha. The spontaneous staggerer (sg/sg) mutation is a deletion in the Rora gene that prevents the translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. The homozygous Rora(sg/sg) mutant mouse, of which the most obvious phenotype is ataxia associated with cerebellar degeneration, also displays a variety of other phenotypes, including several vascular ones; in particular, dysfunction of smooth muscle cells and enhanced susceptibility to atherosclerosis. Moreover, RORalpha appears to participate in the regulation of plasma cholesterol levels, and has been shown to positively regulate apolipoprotein (apo)A-I and apoC-III gene expression. Yet its activity is regulated by cholesterol itself, making RORalpha an intracellular cholesterol target.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk