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(Circulation Research. 1999;85:562-563.)
© 1999 American Heart Association, Inc.

Editorials

Dual Role of Reactive Oxygen Species in Vascular Growth

Kathy K. Griendling, David G. Harrison

From the Division of Cardiology, Emory University, Atlanta, Ga.

Correspondence to Kathy K. Griendling, PhD, Emory University, Division of Cardiology, 1639 Pierce Dr, 319 WMB, Atlanta, GA 30322. E-mail kgriend@emory.edu

Key Words: vascular smooth muscle • hydrogen peroxide • apoptosis • superoxide • proliferation

	Introduction

 
In the last decade, it has become clear that virtually all mammalian cells produce reactive oxygen species. It was generally believed that these were by-products of cellular respiration and metabolism, and that they exerted toxic effects, including DNA damage and lipid oxidation. Recent evidence has demonstrated that this concept is incorrect, and that reactive oxygen species are produced in a controlled fashion and likely have critical signaling functions. Likewise, antioxidant defenses play a crucial role in modulating the ambient steady-state levels of reactive oxygen species. Biological or pharmacological manipulation of endogenous antioxidants can have a profound effect on cellular function.

Emerging evidence suggests that hydrogen peroxide (H₂O₂) plays a particularly important role in signal transduction. H₂O₂ is uncharged and is freely diffusible within and between cells. Compared with other reactive oxygen species, it is also quite stable. A major source of H₂O₂ is a membrane-bound NADH/NADPH oxidase, the activity of which is regulated by hormones, growth factors, and physical forces. The primary product of this enzyme system is superoxide (O₂^·-), which is rapidly dismutated to H₂O₂ by the superoxide dismutases. Removal of H₂O₂ is regulated by two important enzymes, catalase and glutathione peroxidase. Reaction products of H₂O₂, including lipid hydroperoxides, are also biologically active.

Given the fact that the molecule is diffusible and stable and that its production and removal are highly regulated, H₂O₂ is an obvious candidate as a second messenger. Indeed, many studies have demonstrated that H₂O₂ . . . [Full Text of this Article]

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