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(Circulation Research. 2001;88:5.)
© 2001 American Heart Association, Inc.

Editorials

Transforming Growth Factor-ß (TGF-ß) and Vascular Disease: CARP as a Putative TGF-ß Target Gene in the Vessel Wall

James N. Topper

From COR Therapeutics Inc, South San Francisco, Calif.

Correspondence to James N. Topper, MD, PhD, Vice President, Biology, COR Therapeutics Inc, 256 E Grand Ave, South San Francisco, CA 94080. E-mail jtopper@corr.com

Key Words: transforming growth factor-ß • Smad proteins • cardiac ankyrin repeat protein • vascular smooth muscle

	Introduction

 
The transforming growth factor-ß (TGF-ß) superfamily of growth factors and cytokines consists of multiple isoforms of TGF-ß, bone morphogenetic proteins (BMPs), activins, and many other structurally related proteins in vertebrates. Through the work of many investigators, there is increasing evidence to support a role for members of this family in a broad range of biological processes, including the pathogenesis of chronic vascular diseases.¹ For example, TGF-ß₁ is a powerful and essential immune regulator in the vascular system, capable of modulating inflammatory events. This is most dramatically illustrated by the phenotype of mice that lack the gene for the TGF-ß₁ isoform and die in utero or in the perinatal period because of widespread, uncontrolled inflammation, an effect that can be reversed by the systemic administration of active soluble TGF-ß₁.² Conversely, the dysregulated actions of TGF-ß (such as in the presence of excessive amounts of active TGF-ß₁ ligand) are reproducibly associated with the pathological accumulation of excessive extracellular matrix, and this phenomenon has been proposed to play a central role in the pathogenesis of disorders such as hypertensive vascular diseases and diabetic renal disease.³ TGF-ß is a potent regulator of the cell cycle in many cell types, including vascular smooth muscle cells (VSMCs) and endothelial cells, and, as a result, this growth factor has been postulated to play an important, although largely undefined, role in vascular proliferative disorders. Alterations in the levels (either circulating or within the vessel wall) of active TGF-ß₁, a soluble form of endoglin (a cell-surface molecule . . . [Full Text of this Article]

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