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(Circulation Research. 2001;88:1223.)
© 2001 American Heart Association, Inc.

Editorial

Ref-1 and Transcriptional Control of Endothelial Apoptosis

Nanping Wang, Michael B. Stemerman

From the Division of Biomedical Sciences, University of California, Riverside, Calif.

Correspondence to Michael B. Stemerman, MD, Division of Biomedical Sciences, University of California Riverside, Riverside, CA 92521. E-mail michael.stemerman@ucr.edu

Key Words: endotheliumapoptosis • transcription factor • oxidative stress

Vascular endothelium, when unperturbed, provides a surface to the blood vessel, which is passive to the development of thrombosis, and potentially adherent blood cells. This characteristic is the quintessence of vascular homeostasis.¹ However, endothelial cells (ECs) can undergo apoptosis in vitro in response to a variety of pathophysiological conditions including hypoxia, proinflammatory cytokines, bacterial endotoxins, and atherogenic risk factors such as homocysteine and lipoproteins (reviewed in Stefanec² and Dimmeler and Zeiher³ ). These cellular perturbations have in common the generation of intracellular reactive oxygen intermediates, referred to as oxidative stress. ECs respond to these adverse conditions by altering their intracellular reduction/oxidization (redox) state and making their ultimate decision between adaptation (survival) and apoptosis (see Figure). Understanding the precise mechanisms controlling such a process is an important component to our knowledge of cardiovascular diseases. In this issue of Circulation Research, Hall et al⁴ provide novel evidence for a critical role of Ref-1, a redox-sensitive regulator, in affecting EC apoptosis.

View larger version (24K): [in this window] [in a new window]   Figure 1. Role of Ref-1 in endothelial apoptosis. Various pathophysiological conditions cause oxidative stress and intracellular redox change in ECs. Diverse signaling pathways activate transcription factors in both a cell type– and context-specific manner. Successive regulation of pro- or antiapoptotic gene expression controls EC apoptosis or survival. As a DNA repair protein (exhibiting 5'AP-endonuclease activity and 3'-phosphodiesterase) and a regulator of transcription (via redox-based activation of transcription factors (eg, AP-1, p53, and NF-B), Ref-1 may play a pivotal role in modulating EC fate under oxidative stress.

Ref-1 was cloned as Redox . . . [Full Text of this Article]

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