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(Circulation Research. 2002;90:749.)
© 2002 American Heart Association, Inc.

Editorials

Vascular Biology

Look What We Staggered Into

Frank M. Faraci

From the Departments of Medicine and Pharmacology, Cardiovascular Center, University of Iowa College of Medicine, Iowa City, Iowa.

Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242-1081. E-mail frank-faraci@uiowa.edu

Key Words: genetically altered mice • inflammation • blood pressure • vascular muscle

The nuclear receptor superfamily, which includes receptors for steroid hormones, eicosanoids, and retinoic acid, is a group of ligand-dependent transcription factors.¹ Included in this family are "orphan" receptors for which regulatory ligands have yet to be defined (Figure). One such group is the retinoid-related orphan receptor (ROR) subfamily, which has three known members (ROR, RORß, and ROR). Previous work has suggested that RORs are involved in diverse processes including embryonic development as well as cell differentiation, cell proliferation, and cancer.¹

View larger version (21K): [in this window] [in a new window]   Schematic summary of known influences of ROR in vascular biology. The transcription factor ROR is activated by ligands that are presently unknown. Stimuli that regulate expression of ROR are only beginning to be defined (see text). It is also possible that ROR may be constitutively active in some cell types. ROR interacts and binds with ROR-response elements (RORE), which then influence transcriptional activity of ROR-sensitive target genes. Studies to date, including the present study by Besnard et al,5 suggest that ROR target genes influence several prominent vascular phenotypes including vascular inflammation and development of atherosclerosis, expression of contractile proteins, and regulation of vascular tone (vasodilation and vasoconstriction).

Much less is known regarding potential roles for RORs in the cardiovascular system. ROR mRNA is expressed constitutively in human endothelium and vascular muscle in culture as well as within the wall of intact arteries.^2,3 The constitutive levels of ROR mRNA are reduced in human atherosclerotic plaques.³ Several proinflammatory stimuli—interleukin-1ß, TNF, and lipopolysaccharide—all increase ROR mRNA expression . . . [Full Text of this Article]

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