Differential expression of PPARγ by pioglitazone and telmisartan causes effect of disparity on mTORC2-mediated cell

Seul Gi Kim1,2, Jin Young Sung1,2, So-Young Park3,2

  • 1Department of Pharmacology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-Gu, Daegu, 42415, Republic of Korea.

Scientific Reports
|July 2, 2025
PubMed

Insights

Full PPARγ agonists like pioglitazone inhibit mTORC2 signaling, reducing vascular smooth muscle cell proliferation and migration to protect against atherosclerosis. Partial agonists show different effects.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Pharmacology

Background:

  • Vascular smooth muscle cell (VSMC) proliferation and migration contribute to atherosclerotic plaque formation.
  • Peroxisome proliferation-activated receptor gamma (PPARγ) exhibits atheroprotective effects, but its anti-proliferative mechanism in VSMCs requires further elucidation.

Purpose of the Study:

  • To investigate the distinct effects of full and partial PPARγ agonists on VSMC proliferation and migration in the context of atherosclerosis suppression.

Main Methods:

  • Activation of PPARγ using pioglitazone (full agonist) and telmisartan (partial agonist).
  • Assessment of mTORC2 signaling pathway activity.
  • Evaluation of VSMC contractile markers, cell migration, and lipid accumulation.
  • Analysis of differential PPARγ expression patterns.

Main Results:

  • Pioglitazone significantly decreased PDGF-BB-induced mTORC2 signaling, VSMC proliferation, contractile marker expression, migration, and lipid accumulation.
  • Telmisartan, despite activating PPARγ, did not affect mTORC2 signaling, VSMC phenotype switching, or lipid droplet markers.
  • Differential PPARγ expression was identified between pioglitazone and telmisartan treatments, influencing VSMC phenotype and atherosclerosis.

Conclusions:

  • PPARγ activation by full agonists, such as pioglitazone, suppresses VSMC proliferation and migration via inhibition of mTORC2 signaling, conferring an atheroprotective effect.
  • Full and partial PPARγ agonists exert distinct mechanistic effects on VSMC phenotype switching and atherosclerosis progression.

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