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(Circulation Research. 2007;101:985.)
© 2007 American Heart Association, Inc.

Molecular Medicine

Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47^phox Gene Expression in Response to Angiotensin II

Weihua Ni, Yumei Zhan, Huamei He, Elizabeth Maynard, James A. Balschi, Peter Oettgen

From the Division of Cardiology (W.N., Y.Z., E.M., P.O.), Beth Israel Deaconess Medical Center, Boston, Mass, and NMR Laboratory for Physiological Chemistry (H.H., J.A.B.), Brigham and Women’s Hospital, Boston, Mass. H.H. is currently at the Department of Anesthesiology, Children’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Peter Oettgen, MD, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA 02115. E-mail joettgen{at}bidmc.harvard.edu

Angiotensin (Ang) II is a potent mediator of vascular inflammation. A central mechanism by which Ang II promotes inflammation is through the generation of reactive oxygen species (ROS). In the current study, we investigated the role of the transcription factor Ets-1 in regulating Ang II–induced ROS generation. ROS generation was measured in the thoracic aorta of Ets-1^–/– mice compared with littermate controls after continuous infusion of Ang II. H₂O₂ and superoxide anion (O₂^–) production were significantly blunted in the Ets-1^–/– mice. Inhibition of Ets-1 expression by small interfering RNA in primary human aortic smooth muscle cells also potently inhibited ROS production and the induction of the NAD(P)H oxidase subunit p47^phox in response to Ang II. To evaluate the therapeutic potential of inhibiting Ets-1 in wild-type mice, dominant negative Ets-1 membrane-permeable peptides were administered systemically. Ang II–induced ROS production and medial hypertrophy in the thoracic aorta were markedly diminished as a result of blocking Ets-1. In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47^phox.

Key Words: ETS factor • Ets-1 • vascular inflammation • transcription factor

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Targeting NAD(P)H Oxidase: Ets-1 Regulates p47^phox

Takeshi Adachi, Michiko Yamamoto, and Makoto Suematsu
Circ. Res. 2007 101: 962-964. [Extract] [Full Text] [PDF]

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