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PPAR-gamma inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1

Karim Benkirane1, Farhad Amiri, Quy N Diep

  • 1Clinical Institute of Health Research Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

American Journal of Physiology. Heart and Circulatory Physiology
|September 13, 2005
PubMed

Insights

Peroxisome proliferator-activated receptor (PPAR)-gamma activators inhibit angiotensin II-induced vascular smooth muscle cell growth. These activators reduce DNA synthesis and key signaling pathways, potentially aiding hypertension treatment.

Area of Science:

  • Cardiovascular Biology
  • Molecular Pharmacology
  • Cell Signaling

Background:

  • Hypertension involves vascular remodeling driven by angiotensin II (ANG II).
  • PPAR-gamma activators are explored for therapeutic potential in cardiovascular diseases.

Purpose of the Study:

  • To investigate the effects of PPAR-gamma activators on ANG II-induced signaling and vascular smooth muscle cell (VSMC) growth.
  • To elucidate the molecular mechanisms underlying PPAR-gamma's influence on VSMC proliferation.

Main Methods:

  • Rat mesenteric artery VSMCs were treated with ANG II and PPAR-gamma activators (15d-PGJ2, rosiglitazone).
  • Effects on DNA synthesis, signaling pathway activation (ERK1/2, Akt, 4E-BP1, SHIP2), and receptor expression were assessed.
  • AT1 and AT2 receptor blockers (valsartan, PD-123319) were used to delineate receptor involvement.

Main Results:

  • Both 15d-PGJ2 and rosiglitazone significantly decreased ANG II-induced DNA synthesis in VSMCs.
  • PPAR-gamma activation reduced ANG II-induced peak activity of ERK1/2 and Akt pathways, mediated via the AT1 receptor.
  • Rosiglitazone inhibited ANG II-enhanced phosphorylation of 4E-binding protein 1 (4E-BP1) and Src homology (SH) 2-containing inositol phosphatase 2 (SHIP2).

Conclusions:

  • PPAR-gamma activation effectively inhibits ANG II-induced VSMC proliferation by modulating ERK1/2, Akt, 4E-BP1, and SHIP2 signaling.
  • These findings suggest that PPAR-gamma activators hold promise for treating vascular remodeling associated with hypertension.

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