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(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

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