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Updated: May 26, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 gene therapy modulates signal transduction in the apoptotic and cell cycle pathways downregulating neointimal

Theresa Jacob1, Anil Hingorani, Enrico Ascher

  • 1Department of Surgery, Maimonides Medical Center, Brooklyn, NY 11219, USA. tjacob@maimonidesmed.org

Vascular and Endovascular Surgery
|December 14, 2011
PubMed
Abstract

Insights

p53 gene therapy inhibits intimal hyperplasia by activating downstream genes. This process involves cell cycle arrest, DNA repair, and apoptosis, offering a novel therapeutic approach for vascular diseases.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Gene Therapy

Background:

  • Intimal hyperplasia (IH) is a major cause of vascular graft failure.
  • Understanding the molecular mechanisms of IH is crucial for developing effective treatments.
  • p53 gene therapy has shown potential in inhibiting IH.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying p53 gene therapy-induced inhibition of intimal hyperplasia (IH).
  • To elucidate the role of p53 in regulating key cellular processes involved in IH.

Main Methods:

  • In vivo p53 gene transfer using adenovirus in balloon-injured rat carotid arteries.
  • Immunohistochemistry to assess the expression of p53, p21, retinoblastoma protein (Rb), B-cell lymphoma 2 (Bcl-2), Bax, and Bcl-x.
  • Determination of cyclin D1, Fas/CD95, and poly(ADP-ribose)polymerase (PARP) expression.

Main Results:

  • Increased nuclear p53 expression in vascular smooth muscle cells (VSMCs) of treated animals.
  • Significant upregulation of Bax, Bcl-x, p21, and Rb in p53-treated arteries.
  • Decreased PARP and increased Fas expression, with limited Bcl-2 in neointima of untreated controls.

Conclusions:

  • p53 gene transfer effectively inhibits IH by activating downstream effector genes.
  • The mechanism involves promoting cell cycle arrest, DNA repair, and apoptosis.
  • p53 gene therapy represents a promising strategy for managing vascular proliferative diseases.

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