PPAR-γ inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1
Open Access
- 1 January 2006
- journal article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 290 (1) , H390-H397
- https://doi.org/10.1152/ajpheart.00662.2005
Abstract
The present study evaluated the effects of peroxisome proliferator-activated receptor (PPAR)-γ activators on ANG II-induced signaling pathways and cell growth. Vascular smooth muscle cells (VSMC) derived from rat mesenteric arteries were treated with ANG II, with/without the AT1 receptor blocker valsartan or the AT2 receptor blocker PD-123319, after pretreatment for 24 h with the PPAR-γ activators 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) or rosiglitazone. Both 15d-PGJ2 and rosiglitazone decreased ANG II-induced DNA synthesis. Rosiglitazone treatment increased nuclear PPAR-γ expression and activity in VSMC. However, rosiglitazone did not alter expression of PPAR-α/β, ERK 1/2, Akt, or ANG II receptors. 15d-PGJ2 and rosiglitazone decreased ERK 1/2 and Akt peak activity, both of which were induced by ANG II via the AT1 receptor. Rosiglitazone inhibited ANG II-enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), as well as Src homology (SH) 2-containing inositol phosphatase 2 (SHIP2). PPAR-γ activation reduced ANG II-induced growth associated with inhibition of ERK 1/2, Akt, 4E-BP1, and SHIP2. Modulation of these pathways by PPAR-γ activators may contribute to regression of vascular remodeling in hypertension.Keywords
This publication has 41 references indexed in Scilit:
- Obesity, hypertension and insulin resistanceActa Diabetologica, 2005
- The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and diseaseJournal of Molecular and Cellular Cardiology, 2004
- Peroxisome Proliferator-Activated ReceptorsHypertension, 2003
- Akt Is a Major Downstream Target of PI3-Kinase Involved in Angiotensin II–Induced ProliferationHypertension, 2003
- Peroxisome Proliferator-Activated Receptor (PPAR) α and PPARβ/δ, but not PPARγ, Modulate the Expression of Genes Involved in Cardiac Lipid MetabolismCirculation Research, 2003
- Insulin-Induced Akt Activation Is Inhibited by Angiotensin II in the Vasculature Through Protein Kinase C-αHypertension, 2003
- Angiotensin II inhibits insulin-stimulated phosphorylation of eukaryotic initiation factor 4E-binding protein-1 in proximal tubular epithelial cellsBiochemical Journal, 2001
- Increased Expression of Peroxisome Proliferator-Activated Receptor-α and -γ in Blood Vessels of Spontaneously Hypertensive RatsHypertension, 2001
- Src Is an Important Mediator of Extracellular Signal–Regulated Kinase 1/2–Dependent Growth Signaling by Angiotensin II in Smooth Muscle Cells From Resistance Arteries of Hypertensive PatientsHypertension, 2001
- Angiotensin II stimulates DNA and protein synthesis in vascular smooth muscle cells from human arteriesJournal Of Hypertension, 1999