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(Hypertension. 2006;48:671.)
© 2006 American Heart Association, Inc.

Original Articles

Attenuation of Inflammatory Vascular Remodeling by Angiotensin II Type 1 Receptor–Associated Protein

Akira Oshita; Masaru Iwai; Rui Chen; Ayumi Ide; Midori Okumura; Shiori Fukunaga; Toyofumi Yoshii; Masaki Mogi; Jitsuo Higaki; Masatsugu Horiuchi

From the Department of Molecular and Cellular Biology (A.O., M.I., R.C., A.I., M.O., S.F., M.M., M.H.), Division of Medical Biochemistry and Cardiovascular Biology, and Second Department of Internal Medicine (A.O., T.Y., J.H.), Ehime University School of Medicine, Tohon, Ehime, Japan.

Correspondence to Masatsugu Horiuchi, Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan. E-mail horiuchi{at}m.ehime-u.ac.jp

To explore the role of angiotensin II Type 1 receptor–associated protein (ATRAP) in vascular remodeling, we developed transgenic mice for mouse ATRAP cDNA and examined remodeling after inflammatory vascular injury induced by polyethylene cuff placement. In ATRAP transgenic (ATRAP-Tg) mice, ATRAP mRNA was increased 3- to 4-fold in the heart, aorta, and femoral artery. ATRAP-Tg mice showed no significant change in body weight, systolic blood pressure, heart rate, and heart/body weight ratio. However, cell proliferation and neointimal formation in the injured artery were attenuated in ATRAP-Tg mice. The increase in NADPH oxidase activity and the expression of p22^phox, a reduced nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide phosphate oxidase subunit, after cuff placement was also attenuated in ATRAP-Tg mice. Moreover, activation of extracellular signal–regulated kinase, signal transducer and activator of transcription 1, and signal transducer and activator of transcription 3 after cuff placement was significantly reduced in ATRAP-Tg mice. Pressor response and cardiac hypertrophy induced by angiotensin II infusion and pressure overload were also attenuated in ATRAP-Tg mice. These results suggest that ATRAP plays an important role in vascular remodeling as a negative regulator.

Key Words: receptors, angiotensin II • signal transduction • vascular diseases • muscle, smooth, vascular

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