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Interferon regulatory factor-1 mediates PPARgamma-induced apoptosis in vascular smooth muscle cells

Yiming Lin1, Xiaojun Zhu, Farron L McLntee

  • 1Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 6, 2003
PubMed
Abstract

Insights

Interferon regulatory factor-1 (IRF-1) mediates beneficial cardiovascular effects of peroxisome proliferator-activated receptor gamma (PPARgamma) by inducing apoptosis in vascular smooth muscle cells (VSMCs). This study identifies IRF-1 as a novel PPARgamma target gene.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Cell Biology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) has known cardiovascular benefits, including inhibiting vascular lesion formation and atherosclerosis.
  • The precise molecular mechanisms underlying PPARgamma's cardioprotective effects remain incompletely understood.

Purpose of the Study:

  • To investigate whether interferon regulatory factor-1 (IRF-1), a transcription factor with anti-proliferative and pro-apoptotic properties, mediates PPARgamma-induced apoptosis in vascular smooth muscle cells (VSMCs).

Main Methods:

  • Utilized Northern and Western blot analyses to assess IRF-1 expression in VSMCs.
  • Employed PPARgamma ligands and antagonists (ciglitazone, troglitazone, GW7845, GW9662) to study gene regulation.
  • Investigated IRF-1 promoter activity and mRNA stability.
  • Used adenoviral expression and antisense technology to manipulate IRF-1 levels.

Main Results:

  • PPARgamma ligands significantly increased IRF-1 expression in VSMCs, an effect blocked by the PPARgamma antagonist GW9662.
  • PPARgamma activation enhanced IRF-1 promoter activity but did not alter mRNA stability.
  • Reduced IRF-1 expression attenuated PPARgamma-induced VSMC apoptosis, decreasing p21(cip1) and caspase-3 activity.

Conclusions:

  • Interferon regulatory factor-1 (IRF-1) is identified as a novel target gene of PPARgamma.
  • IRF-1 mediates the pro-apoptotic effects of PPARgamma in vascular smooth muscle cells, contributing to its cardiovascular benefits.

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