Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia

Jianhua Huang, Xi Lin Niu, Anne M. Pippen, Brian H. Annex, Christopher D. Kontos

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)354-358
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Neointimal hyperplasia
  • PTEN
  • Phosphoinositide 3-kinase
  • Vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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