Open AccessAttenuation of Inflammatory Vascular Remodeling by Angiotensin II Type 1 Receptor–Associated Protein
Author(s) -
Akira Oshita,
Masaru Iwai,
Rui Chen,
Akio Ide,
Midori Okumura,
Shiori Fukunaga,
Toshitaka Yoshii,
Masaki Mogi,
Jitsuo Higaki,
Masatsugu Horiuchi
Publication year - 2006
Publication title -
hypertension
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.986
H-Index - 265
eISSN - 1524-4563
pISSN - 0194-911X
DOI - 10.1161/01.hyp.0000238141.99816.47
Subject(s) - nicotinamide adenine dinucleotide phosphate , medicine , angiotensin ii , endocrinology , biology , blood pressure , oxidase test , biochemistry , enzyme
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 p22phox , 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.