title: p53 gene therapy modulates signal transduction in the apoptotic and cell cycle pathways downregulating neointimal hyperplasia.
abstract: OBJECTIVE
  To investigate the molecular mechanisms that lead to inhibition of intimal hyperplasia (IH) following p53 gene therapy.
  
  
  METHODS
  In vivo p53 gene transfer to balloon injured rat carotid arteries was performed by utilizing adenovirus. The relationship between p53, p21, retinoblastoma protein (Rb), B-cell lymphoma 2 (Bcl-2), Bax, and Bcl-x was examined by immunohistochemistry. Expression of cyclin D1, Fas/CD95, and poly(ADP-ribose)polymerase (PARP) was determined.
  
  
  RESULTS
  Our data indicate increased expression of p53 in the nuclei of vascular smooth muscle cells (VSMCs) in the media (P < .01) compared with the controls. In the treated animals, Bax and Bcl-x, p21, and Rb were significantly upregulated (P < .01). Immunoreactivity to Bcl-2 was observed only in the neointima of untreated groups at 14 days. An increased presence of Fas and decreased expression of PARP was observed in the cytoplasm of the VSMCs of p53-treated animals.
  
  
  CONCLUSIONS
  P53 gene transfer activated a battery of downstream effector genes whose products are directly involved in cell cycle arrest, DNA repair, and apoptosis.
authors.affiliation: Department of Surgery, Maimonides Medical Center, Brooklyn, NY 11219, USA. tjacob@maimonidesmed.org
authors.forename: Theresa
authors.initials: T
authors.lastname: Jacob
authors.forename: Anil
authors.initials: A
authors.lastname: Hingorani
authors.forename: Enrico
authors.initials: E
authors.lastname: Ascher
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology*; D002404:Catheterization; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism; D004260:DNA Repair; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D058426:Neointima / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D057772:Vascular System Injuries / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53