PMID- 26471325
OWN - NLM
STAT- MEDLINE
DCOM- 20171220
LR  - 20180628
IS  - 1941-7225 (Electronic)
IS  - 0895-7061 (Linking)
VI  - 29
IP  - 6
DP  - 2016 Jun
TI  - Angiotensin II Type 2 Receptor Inhibits Vascular Intimal Proliferation With 
      Activation of PPARgamma.
PG  - 727-36
LID - 10.1093/ajh/hpv168 [doi]
AB  - BACKGROUND: Angiotensin II type 2 (AT2) receptor stimulation could exert 
      beneficial effects on vascular remodeling. Previously, we reported that AT2 
      receptor stimulation ameliorated insulin resistance in diabetic mice accompanied 
      by PPARgamma activation which also plays a variety of crucial roles in the 
      vasculature. Therefore, this study aimed to investigate the vascular protective 
      effect of the AT2 receptor with activation of PPARgamma involving AT2 
      receptor-interacting protein (ATIP). METHODS AND RESULTS: Vascular injury was 
      induced by polyethylene-cuff placement around the femoral artery in C57BL/6J 
      mice. Treatment with compound 21 (C21), an AT2 receptor agonist, decreased 
      neointimal formation, cell proliferation, and the mRNA levels of monocyte 
      chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-alpha, and 
      interleukin-1beta, and phosphorylation of nuclear factor-kappa B, and increased 
      PPARgamma DNA-binding activity in the injured artery, whereas these inhibitory 
      effects of C21 were attenuated by co-treatment with a PPARgamma antagonist, GW9662. 
      Treatment of vascular smooth muscle cells (VSMC) with C21 prepared from smAT2 
      transgenic mice, which highly express the AT2 receptor in VSMC, increased both 
      PPARgamma activity and its DNA-binding activity determined by dual-luciferase assay 
      and electrophoresis mobility shift assay (EMSA), respectively. We observed that 
      ATIP was involved in PPARgamma complex formation, and that transfection of siRNA of 
      ATIP1 attenuated the AT2 receptor-mediated increase in PPARgamma activity in VSMC. In 
      response to AT2 receptor stimulation, ATIP was translocated from the plasma 
      membrane to the nucleus. CONCLUSIONS: Our results suggest a new mechanism by 
      which AT2 receptor stimulation activates PPARgamma, thereby resulting in amelioration 
      of vascular intimal proliferation, and that ATIP plays an important role in AT2 
      receptor-mediated PPARgamma activation.
CI  - (c) American Journal of Hypertension, Ltd 2015. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Kukida, Masayoshi
AU  - Kukida M
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan; Department of 
      Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University, Graduate 
      School of Medicine, Tohon, Ehime, Japan;
FAU - Mogi, Masaki
AU  - Mogi M
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan; 
      mmogi@m.ehime-u.ac.jp.
FAU - Ohshima, Kousei
AU  - Ohshima K
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan; Department of 
      Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University, Graduate 
      School of Medicine, Tohon, Ehime, Japan;
FAU - Nakaoka, Hirotomo
AU  - Nakaoka H
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Iwanami, Jun
AU  - Iwanami J
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Kanno, Harumi
AU  - Kanno H
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Tsukuda, Kana
AU  - Tsukuda K
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Chisaka, Toshiyuki
AU  - Chisaka T
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan; Department of 
      Pediatrics, Ehime University, Graduate School of Medicine, Tohon, Ehime, Japan.
FAU - Min, Li-Juan
AU  - Min LJ
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Wang, Xiao-Li
AU  - Wang XL
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Bai, Hui-Yu
AU  - Bai HY
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Shan, Bao-Shuai
AU  - Shan BS
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Higaki, Akinori
AU  - Higaki A
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan; Department of 
      Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University, Graduate 
      School of Medicine, Tohon, Ehime, Japan;
FAU - Yamauchi, Toshifumi
AU  - Yamauchi T
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan; Department of 
      Pediatrics, Ehime University, Graduate School of Medicine, Tohon, Ehime, Japan.
FAU - Okura, Takafumi
AU  - Okura T
AD  - Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Higaki, Jitsuo
AU  - Higaki J
AD  - Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
FAU - Horiuchi, Masatsugu
AU  - Horiuchi M
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan;
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151015
PL  - United States
TA  - Am J Hypertens
JT  - American journal of hypertension
JID - 8803676
RN  - 0 (Carrier Proteins)
RN  - 0 (Mtus1 protein, mouse)
RN  - 0 
      (N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiophenes)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Myocytes, Smooth Muscle/metabolism
MH  - *Neointima
MH  - PPAR gamma/*metabolism
MH  - Receptor, Angiotensin, Type 2/*metabolism
MH  - Sulfonamides
MH  - Thiophenes
MH  - Tumor Suppressor Proteins/*metabolism
MH  - *Vascular Remodeling
OTO - NOTNLM
OT  - ATIP
OT  - PPARgamma
OT  - angiotensin II type 2 receptor
OT  - blood pressure
OT  - hypertension
OT  - vascular remodeling.
EDAT- 2015/10/17 06:00
MHDA- 2017/12/21 06:00
CRDT- 2015/10/17 06:00
PHST- 2015/06/18 00:00 [received]
PHST- 2015/09/24 00:00 [accepted]
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2017/12/21 06:00 [medline]
AID - hpv168 [pii]
AID - 10.1093/ajh/hpv168 [doi]
PST - ppublish
SO  - Am J Hypertens. 2016 Jun;29(6):727-36. doi: 10.1093/ajh/hpv168. Epub 2015 Oct 15.