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Effects of a PPAR-gamma agonist, on growth factor and insulin stimulated endothelial cells

Cyrus V Desouza1, Moira Gerety, Frederick G Hamel

  • 1Omaha Veterans Affairs Medical Center, United States; University of Nebraska Medical Center, United States. cdesouza@unmc.edu

Vascular Pharmacology
|June 13, 2009
PubMed
Abstract

Insights

Pioglitazone, a PPAR-gamma agonist, may harm cardiovascular health post-angioplasty by inhibiting endothelial regrowth. This occurs through reduced VEGF/FGF signaling, potentially increasing risks in insulin-resistant patients.

Area of Science:

  • Cardiovascular Research
  • Endothelial Biology
  • Pharmacology

Background:

  • PPAR-gamma agonists like thiazolidinediones are used for insulin resistance.
  • Concerns exist regarding increased cardiovascular risk with some thiazolidinediones.
  • Animal studies suggest impaired endothelial regrowth as a potential mechanism for adverse effects.

Purpose of the Study:

  • To investigate the effect of pioglitazone on endothelial cells stimulated by VEGF, FGF, and insulin.
  • To determine if pioglitazone inhibits endothelial regrowth by affecting key signaling pathways.

Main Methods:

  • In vitro study using human umbilical vein endothelial cells (HUVECs).
  • Assessed proliferation and apoptosis under various conditions: VEGF/FGF stimulation, hyperinsulinemia, and pioglitazone treatment.
  • Measured activation of ERK 1/2 and p38MAPK signaling pathways.

Main Results:

  • Pioglitazone decreased VEGF-stimulated HUVEC proliferation by 40%, an effect reversed by insulin.
  • Pioglitazone reduced ERK 1/2 activation in VEGF-stimulated cells, partially reversed by insulin.
  • Pioglitazone increased endothelial cell apoptosis and p38MAPK activation.

Conclusions:

  • PPAR-gamma agonists may pose cardiovascular risks after angioplasty, particularly in insulin-resistant individuals.
  • Pioglitazone's inhibition of VEGF/FGF-stimulated ERK 1/2 pathways may impair endothelial regrowth and re-endothelialization.
  • These findings suggest a mechanism for detrimental cardiovascular effects of pioglitazone.

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