PPAR- inhibits ANG II-induced cell growth via SHIP2 and 4E-BP1
نویسندگان
چکیده
Benkirane, Karim, Farhad Amiri, Quy N. Diep, Mohammed El Mabrouk, and Ernesto L. Schiffrin. PPARinhibits ANG IIinduced cell growth via SHIP2 and 4E-BP1. Am J Physiol Heart Circ Physiol 290: H390–H397, 2006. First published September 9, 2005; doi:10.1152/ajpheart.00662.2005.—The present study evaluated the effects of peroxisome proliferator-activated receptor (PPAR)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 PPARactivators 15-deoxyprostaglandin J2 (15d-PGJ2) or rosiglitazone. Both 15d-PGJ2 and rosiglitazone decreased ANG II-induced DNA synthesis. Rosiglitazone treatment increased nuclear PPARexpression and activity in VSMC. However, rosiglitazone did not alter expression of PPAR/ , 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). PPARactivation reduced ANG II-induced growth associated with inhibition of ERK 1/2, Akt, 4EBP1, and SHIP2. Modulation of these pathways by PPARactivators may contribute to regression of vascular remodeling in hypertension.
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