Attenuation of cuff-induced neointimal formation by overexpression of angiotensin II type 2 receptor-interacting protein 1

Hypertension. 2009 Apr;53(4):688-93. doi: 10.1161/HYPERTENSIONAHA.108.128140. Epub 2009 Feb 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Arterial Occlusive Diseases / metabolism*
  • Arterial Occlusive Diseases / pathology
  • Arterial Occlusive Diseases / physiopathology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Division / physiology
  • Femoral Artery / pathology
  • Femoral Artery / physiology
  • Gene Expression / physiology
  • Heart / anatomy & histology
  • Heart / physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Size / drug effects
  • Organ Size / physiology
  • Oxidative Stress / physiology
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Superoxides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*
  • Tunica Intima / pathology
  • Tunica Intima / physiology
  • Vasculitis / metabolism
  • Vasculitis / pathology
  • Vasculitis / physiopathology
  • Vasoconstrictor Agents / pharmacology

Substances

  • Carrier Proteins
  • Mtus1 protein, mouse
  • Receptor, Angiotensin, Type 2
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • Vasoconstrictor Agents
  • Superoxides
  • Angiotensin II