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(Circulation Research. 2000;86:1009.)
© 2000 American Heart Association, Inc.

Editorials

Death Receptors, Intimal Disease, and Gene Therapy

Are Therapies That Modify Cell Fate Moving too Fas?

Gary H. Gibbons, Matthew J. Pollman

From the Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Ga.

Correspondence to Gary H. Gibbons, Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310. E-mail ggibbons@msm.edu

Key Words: apoptosis • Fas • gene therapy • intima

	Introduction

 
The pathogenesis of vascular diseases such as atherosclerosis and postangioplasty restenosis is characterized by endothelial cell injury and an abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal space. The classic paradigm has emphasized the role of VSMC migration, proliferation, and subsequent elaboration of extracellular matrix as the principal cellular events that mediate neointima formation.¹ In accord with this model, gene therapy strategies directed at inhibiting cell proliferation and migration have been shown to be effective at inhibiting intimal disease in animal models and are currently under study as novel therapies for vascular disease in clinical trials.^{2 3 4 5}

It has become increasingly clear that the cellular economy within tissues reflects a balance between cell proliferation and cell death by apoptosis.^{6 7 8} Studies involving both animal models and human specimens have clearly established that VSMC apoptosis is a prominent feature of the response to injury and the consequent formation of the neointima.^{9 10 11} Nevertheless, the studies describing the association between cell death and lesion formation fail to definitively establish the pathogenic role of vascular cell apoptosis in the natural history of intimal vascular disease. Therefore, it remains to be determined whether therapeutic strategies that modulate apoptosis within the vasculature will have efficacy in ameliorating the course of vascular disease. The study by Chan et al¹² in this issue of Circulation Research provides important new insights into the complexities of the intrinsic compensatory mechanisms that VSMCs exhibit to promote cell viability under various conditions. These findings challenge us to develop a deeper, more . . . [Full Text of this Article]

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