ABSTRACT

Introduction 141

Oxidants, Antioxidants, and NF-kB Mediated Gene Expression in the Endothelium 143

Oxidants, Antioxidants, and AP-1 Mediated Gene Expression

in the Endothelium 148

Vitamin E and Endothelial Gene Expression 152

Regulation of Transcription Through Changes in Chromatin Structure 157

Applicability to Physiological Conditions 160

Discussion 164

Conclusion 167

Acknowledgments 167

References 167

INTRODUCTION

Thirty years ago, the main roles of endothelial cells-the cells lining the inner

surface of all blood vessels-were thought to be the largely passive ones of

providing a nonthrombogenic surface and of keeping macromolecules within

plasma, while allowing the exchange of smaller solutes with underlying tissue.

Since then, however, endothelial cells have been shown to play an active and

key role in a large number of physiological processes that are critical for vas-

cular homeostasis (1). The explosion of interest in these cells has undoubtedly

been fueled by their central involvement in the development of atherosclerosis.

This disease underlies most myocardial infarctions and cerebrovascular acci-

dents, and in many countries it constitutes the major cause of death. Several

aspects of its pathogenesis remain to be established but there is currently a con-

sensus that key events include the activation or perturbation of endothelial cells

by various mechanical, chemical, or biological stimuli, entry of lipoproteins

and inflammatory cells into the arterial wall, the migration of smooth muscle

cells (SMC) into the arterial intima and their subsequent proliferation, and

interactions between the atheromatous plaque and circulating platelets, all of

which are strongly influenced by the endothelium (2).