title: Attenuation of cuff-induced neointimal formation by overexpression of angiotensin II type 2 receptor-interacting protein 1.
abstract: Recently we have cloned angiotensin II type 2 receptor-interacting protein 1 (ATIP1) as a novel protein that interacts specifically with the C-terminal tail of the angiotensin II type 2 receptor; however, the pathophysiological roles of ATIP1 in vascular remodeling are still unknown. Here, we generated ATIP1-transgenic (ATIP1-Tg) mice expressing mouse ATIP1 and investigated the role of ATIP1 in vascular remodeling using these transgenic mice. ATIP1-Tg mice exhibited no significant difference in blood pressure compared with wild-type (WT) mice. Angiotensin II type 2 receptor mRNA expression in the femoral artery was increased in injured femoral arteries, reaching a peak at 7 days after operation in WT mice, and a similar result of angiotensin II type 2 receptor expression was observed in ATIP1-Tg mice. In ATIP1-Tg mice, neointimal formation of the femoral artery 14 days after cuff placement was significantly smaller than that in WT mice. 5-Bromo-2'-deoxyuridine incorporation was significantly reduced in the injured arteries of ATIP1-Tg mice compared with WT mice. In ATIP1-Tg mice, superoxide anion production and the expression of a proinflammatory cytokine, tumor necrosis factor-alpha, were markedly attenuated. Moreover, cell proliferative signaling, such as extracellular signal-regulated kinase phosphorylation, was significantly attenuated in ATIP1-Tg mice compared with WT mice. Taken together, these results suggest that ATIP1 plays an important role in cuff-induced vascular remodeling in mice.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Ehime 791-0295, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Fujita
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Min
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Kana
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakata
authors.forename: Hideki
authors.initials: H
authors.lastname: Okayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Clara
authors.initials: C
authors.lastname: Nahmias
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D005263:Femoral Artery / Q000473:pathology / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; C488664:Mtus1 protein, mouse; D044139:Receptor, Angiotensin, Type 2; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II