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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
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Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL

A C Li1, K K Brown, M J Silvestre

  • 1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0651, USA.

The Journal of Clinical Investigation
|August 23, 2000
PubMed

Insights

PPARgamma agonists, like rosiglitazone, significantly reduced atherosclerosis development in mice. These findings suggest potential benefits for diabetic patients, highlighting PPARgamma

Area of Science:

  • Cardiovascular Research
  • Metabolic Disease Research
  • Molecular Pharmacology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates glucose homeostasis and adipogenesis.
  • PPARgamma is implicated in atherosclerosis, with roles in macrophage foam cells.
  • PPARgamma agonists are used to manage type 2 diabetes mellitus.

Purpose of the Study:

  • To investigate the antiatherogenic effects of PPARgamma agonists.
  • To determine the impact of PPARgamma activation on atherosclerosis in a mouse model.
  • To explore the relationship between PPARgamma activity, insulin sensitivity, and inflammatory markers.

Main Methods:

  • Utilized LDL receptor-deficient male mice to model atherosclerosis.
  • Administered PPARgamma-specific agonists (rosiglitazone and GW7845).
  • Assessed atherosclerosis development, CD36 scavenger receptor expression, insulin sensitivity, and tissue expression of TNF-alpha and gelatinase B.

Main Results:

  • PPARgamma agonists strongly inhibited atherosclerosis progression in male mice.
  • Inhibition occurred despite increased CD36 scavenger receptor expression in the arterial wall.
  • Antiatherogenic effects correlated with improved insulin sensitivity and reduced TNF-alpha and gelatinase B expression.

Conclusions:

  • PPARgamma agonists demonstrate significant antiatherogenic effects in a preclinical model.
  • Both systemic and local mechanisms contribute to the antiatherogenic actions of PPARgamma.
  • Findings support the development of PPARgamma ligands with separable antidiabetic and antiatherogenic activities.

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