title: Angiotensin II type 2 receptor-interacting protein prevents vascular senescence.
abstract: Angiotensin II type 2 (AT(2)) receptor-interacting protein (ATIP), which interacts with the C-terminal tail of the AT(2) receptor, regulates the functions of the AT(2) receptor. We have reported that AT(2) receptor stimulation attenuated vascular senescence. Therefore, we examined the possible negative role of ATIP in regulating vascular senescence. We generated ATIP-transgenic (Tg) mice, and cultured vascular smooth muscle cells (VSMCs). Persistent angiotensin II stimulation induced increases in SA-β-gal-positive cells and the level of a DNA damage marker, 8-OHdG in VSMC, whereas these effects of angiotensin II were attenuated in VSMC prepared from ATIP-Tg mice. Angiotensin II treatment also upregulated the expression of methyl methanesulfonate-sensitive 2 (MMS2), a DNA repair factor, and Src homology 2 domain-containing protein-tyrosine phosphatase 1 (SHP-1) activity, whereas these effects of angiotensin II were further enhanced in ATIP-Tg VSMC. In vivo, x-ray irradiation to mice caused increases in SA-β-gal-positive area and 8-OHdG level in the thoracic aorta; however, these effects were reduced in ATIP-Tg mice, with a significant increase in MMS2 expression. These results suggest that ATIP could inhibit VSMC senescence, involving MMS2 expression and SHP-1 activity. ATIP might be a new therapeutic molecule to treat vascular aging and age-related vascular diseases.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Ehime, Japan.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Min
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Fei
authors.initials: F
authors.lastname: Jing
authors.forename: Kana
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Kousei
authors.initials: K
authors.lastname: Ohshima
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D014652:Vascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; C488664:Mtus1 protein, mouse; D044139:Receptor, Angiotensin, Type 2; D025521:Tumor Suppressor Proteins