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Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia.

Publication ,  Journal Article
Huang, J; Niu, X-L; Pippen, AM; Annex, BH; Kontos, CD
Published in: Arterioscler Thromb Vasc Biol
February 2005

OBJECTIVE: Phosphoinositide (PI) 3-kinase promotes vascular smooth muscle cell (VSMC) responses necessary for neointimal hyperplasia. We recently demonstrated that the inositol 3-phosphatase PTEN is expressed in VSMCs and that its overexpression inhibits these cellular responses. The purpose of this study was to determine the effects of adenovirus-mediated overexpression of PTEN on neointimal hyperplasia in vivo in the rat carotid injury model. METHODS AND RESULTS: Rat carotid arteries were balloon-injured and treated with a recombinant control adenovirus (AdEV) (n=6), an adenovirus encoding wild-type PTEN (AdPTEN) (n=8), or phosphate-buffered saline (sham) (n=5). Injured vessels demonstrated PTEN overexpression by Western blotting and immunohistochemistry after AdPTEN treatment. Neointimal hyperplasia was assessed 2 weeks after balloon injury and adenovirus administration. Compared with controls, AdPTEN treatment significantly decreased neointimal area and percent stenosis. To investigate the mechanisms of action of AdPTEN, vessels were harvested 3 days after balloon injury and virus infection. AdPTEN significantly increased medial cell apoptosis while decreasing proliferation of the remaining viable cells. CONCLUSIONS: PTEN overexpression potently inhibits neointimal hyperplasia through induction of apoptosis and inhibition of medial cell proliferation. These findings suggest that modulation of PTEN expression or activity may be a viable approach to treat neointimal hyperplasia. Phosphoinositide (PI) 3-kinase is a critical regulator of neointimal hyperplasia. The inositol 3-phosphatase PTEN modulates PI 3-kinase signaling by hydrolyzing the phospholipid products of PI 3-kinase, and overexpression of PTEN in vascular smooth muscle cells inhibits the cellular processes necessary for neointimal hyperplasia. The effects of adenovirus-mediated PTEN (AdPTEN) overexpression on neointimal hyperplasia were tested in the rat carotid injury model. Compared with control arteries, AdPTEN treatment significantly reduced neointimal area and percent stenosis by enhancing medial cell apoptosis and inhibiting proliferation of the remaining viable cells. Thus, PTEN provides a new target for the treatment of neointimal hyperplasia.

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Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

February 2005

Volume

25

Issue

2

Start / End Page

354 / 358

Location

United States

Related Subject Headings

  • Tunica Intima
  • Tumor Suppressor Proteins
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Rats, Sprague-Dawley
  • Rats
  • Phosphoric Monoester Hydrolases
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
 

Citation

APA
Chicago
ICMJE
MLA
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Huang, J., Niu, X.-L., Pippen, A. M., Annex, B. H., & Kontos, C. D. (2005). Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia. Arterioscler Thromb Vasc Biol, 25(2), 354–358. https://doi.org/10.1161/01.ATV.0000151619.54108.a5
Huang, Jianhua, Xi-Lin Niu, Anne M. Pippen, Brian H. Annex, and Christopher D. Kontos. “Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia.Arterioscler Thromb Vasc Biol 25, no. 2 (February 2005): 354–58. https://doi.org/10.1161/01.ATV.0000151619.54108.a5.
Huang J, Niu X-L, Pippen AM, Annex BH, Kontos CD. Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):354–8.
Huang, Jianhua, et al. “Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia.Arterioscler Thromb Vasc Biol, vol. 25, no. 2, Feb. 2005, pp. 354–58. Pubmed, doi:10.1161/01.ATV.0000151619.54108.a5.
Huang J, Niu X-L, Pippen AM, Annex BH, Kontos CD. Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):354–358.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

February 2005

Volume

25

Issue

2

Start / End Page

354 / 358

Location

United States

Related Subject Headings

  • Tunica Intima
  • Tumor Suppressor Proteins
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Rats, Sprague-Dawley
  • Rats
  • Phosphoric Monoester Hydrolases
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase