Attenuation of inflammatory vascular remodeling by angiotensin II type 1 receptor-associated protein.
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.
Oshita
Akira
A
Department of Molecular and Cellular Biology, Ehime University School of Medicine, Tohon, Ehime, Japan.
Iwai
Masaru
M
Chen
Rui
R
Ide
Ayumi
A
Okumura
Midori
M
Fukunaga
Shiori
S
Yoshii
Toyofumi
T
Mogi
Masaki
M
Higaki
Jitsuo
J
Horiuchi
Masatsugu
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003250:Constriction; D005263:Femoral Artery / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D017539:Tunica Intima / Q000187:drug effects / Q000254:growth & development; D014947:Wounds and Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology
D048868:Adaptor Proteins, Signal Transducing; C119712:Agtrap protein, mouse