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(Circulation Research. 2001;88:7.)
© 2001 American Heart Association, Inc.

Editorials

Control of Vascular Cell Differentiation by Homeiobox Transcription Factors

David H. Gorski, Kenneth Walsh

From the Division of Surgical Oncology (D.H.G.), UMDNJ–Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, NJ, and Division of Cardiovascular Research (K.W.), Tufts University School of Medicine, St Elizabeth’s Medical Center, Boston, Mass.

Correspondence to Kenneth Walsh, PhD, Division of Cardiovascular Research, Tufts University School of Medicine, St Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135. E-mail kwalsh@opal.tufts.edu

Key Words: homeobox genes • vascular smooth muscle

	Introduction

 
Pathological remodeling in the vasculature occurs during the development of restenosis after balloon angioplasty and atherosclerosis, where the migration of proliferating phenotypically modified vascular smooth muscle cells (VSMCs) from the media to the intima is an important contributor to the intimal thickening that narrows the vessel lumen.¹ In the normal vessel wall, VSMCs are in the "contractile" state in that they are quiescent, do not migrate, and express smooth muscle–specific isoforms of contractile proteins.² By contrast, in diseased vessels, VSMCs acquire a "synthetic" state, in which they are proliferative, migratory, and express lower levels of contractile proteins and higher levels of nonmuscle isoforms of myosin and actin. Synthetic VSMCs generally resemble their less-differentiated precursors in fetal blood vessels. Since 1992, investigators have sought to examine what roles homeobox genes may play in controlling the phenotypic modulation of VSMCs.³ First characterized in the study of Drosophila mutations that give rise to homeotic transformations,⁴ homeobox genes encode transcription factors with a common 60 amino acid DNA-binding motif that is referred to as the homeodomain.⁵ These homeodomain-containing transcription factors regulate proliferation, differentiation, and migration in multiple cell types and play an important role in organogenesis and pattern formation during embryogenesis.⁶ These features of homeobox proteins make them promising candidates as regulators of cellular differentiation involved in the final transcriptional control of the genes responsible for the phenotypic changes observed in VSMCs during development and in pathological states.⁷

In this issue of Circulation Research, Sekiguchi et al⁸ report observations suggesting that at least . . . [Full Text of this Article]

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