This Article Full Text Full Text (PDF) All Versions of this Article: 24/4/637    most recent 01.ATV.0000119355.56036.dev1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boukhtouche, F. Articles by Tedgui, A. Search for Related Content PubMed PubMed Citation Articles by Boukhtouche, F. Articles by Tedgui, A. Related Collections Pathophysiology Cell signalling/signal transduction Gene regulation Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:637.)
© 2004 American Heart Association, Inc.

Brief Reviews

The "CholesteROR" Protective Pathway in the Vascular System

Fatiha Boukhtouche; Jean Mariani; Alain Tedgui

From the Laboratoire Développement et Vieillissement du Système Nerveux (F.B., J.M.), Université P. & M. Curie-CNRS, UMR NPA 7102, case 14, 9 quai Saint Bernard, 75005 Paris, France; and U541 INSERM, Hôpital Lariboisière (A.T.), 41 boulevard de la Chapelle, 75475 Paris, France

Correspondence to Alain Tedgui, INSERM U541, 41 boulevard de la Chapelle, 75475 Paris cedex 10, France. E-mail Alain.Tedgui{at}larib.inserm.fr

Retinoic acid receptor-related Orphan Receptor (ROR) is a member of the nuclear hormone receptor superfamily. ROR 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 ROR. 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 ROR 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, ROR 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 ROR an intracellular cholesterol target.

Key Words: ROR • cholesterol • statins • atherosclerosis • lipid homeostasis

This article has been cited by other articles:

				N. Ohoka, S. Kato, Y. Takahashi, H. Hayashi, and R. Sato The Orphan Nuclear Receptor ROR{alpha} Restrains Adipocyte Differentiation through a Reduction of C/EBP{beta} Activity and Perilipin Gene Expression Mol. Endocrinol., June 1, 2009; 23(6): 759 - 771. [Abstract] [Full Text] [PDF]

				T. Sugawara, E. Nomura, and N. Hoshi Cholesterol sulphate affects production of steroid hormones by reducing steroidogenic acute regulatory protein level in adrenocortical cells J. Endocrinol., December 1, 2007; 195(3): 451 - 458. [Abstract] [Full Text] [PDF]

				A. G. Smith and G. E. O. Muscat Orphan nuclear receptors: therapeutic opportunities in skeletal muscle Am J Physiol Cell Physiol, August 1, 2006; 291(2): C203 - C217. [Abstract] [Full Text] [PDF]

				S.-O. Olofsson ApoA-V: The Regulation of a Regulator of Plasma Triglycerides Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1097 - 1099. [Full Text] [PDF]

				B. C. Blaxall, J. M. Miano, and B. C. Berk Angiotensin II: A Devious Activator of Mineralocorticoid Receptor-Dependent Gene Expression Circ. Res., April 1, 2005; 96(6): 610 - 611. [Full Text] [PDF]

				K. Pardee, J. Reinking, and H. Krause Nuclear Hormone Receptors, Metabolism, and Aging: What Goes Around Comes Around Sci. Aging Knowl. Environ., November 24, 2004; 2004(47): re8 - re8. [Abstract] [Full Text] [PDF]