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(Circulation Research. 2007;101:962.)
© 2007 American Heart Association, Inc.

Editorials

Targeting NAD(P)H Oxidase

Ets-1 Regulates p47^phox

Takeshi Adachi, Michiko Yamamoto, Makoto Suematsu

From the Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, Tokyo, Japan.

Correspondence to Takeshi Adachi, MD, PhD, Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, Research Park 4N8, 35 Shinanomachi Shinjuku-ku, Tokyo Japan 160-8582. E-mail tadachi@sc.itc.keio.ac.jp

See related article, pages 985–994

Key Words: Ets-1 • NAD(P)H oxidase • Angiotensin II • hypertension

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Reactive Oxygen Species (ROS) have been shown to modulate vascular signaling in endothelium, smooth muscle, and adventitia, regulate vascular hypertrophy, inflammation, remodeling, intracellular calcium, and disturb nitric oxide bioactivity.^1,2 Since Griendling et al discovered the activation of NAD(P)H oxidase by angiotensin II (Ang II),³ researches have focused on the regulation of this enzyme in Ang II signaling/Ang II-induced hypertension both in vitro and in vivo. Vascular NAD(P)H oxidase consists of multiple subunits including p22^phox, p40^phox, p47^phox, p67^phox, Rac1, and unique catalytic subunits, Nox isoforms (gp91^phox homologue).⁴ The signaling mechanisms for the rapid activation of NAD(P)H oxidase by Ang II have been identified using cultured aortic vascular smooth muscle cells (VSMCs). Ang II rapidly activates PLC to increase intracellular calcium and diacylglycerol levels, which causes the activation of protein kinase C (PKC). PKC phosphorylates p47^phox and releases ROS from Nox subunits. Subsequently, ROS activates cSrc, EGF-receptor, PI3-kinase, and Rac1, leading to the secondary activation of NAD(P)H oxidase to augment the intracellular ROS levels.⁴ These events occur within 30 minutes in cultured VSMCs. Considering the ROS generation associated with hypertension in vivo, the latter transcriptional upregulation of NAD(P)H oxidase subunits by Ang II might be more important. Ang II upregulates the expressions of NAD(P)H oxidase subunits after more than 4 hours including p22^phox, Nox2 (gp91^phox), p47^phox, and p67^phox,⁵ however the mechanisms of transcriptional regulations for NAD(P)H oxidase subunits have not fully been elucidated yet.

In this issue of Circulation Research, Ni and colleagues . . . [Full Text of this Article]

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				W. J. Welch Angiotensin II-Dependent Superoxide: Effects on Hypertension and Vascular Dysfunction Hypertension, July 1, 2008; 52(1): 51 - 56. [Full Text] [PDF]