期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 290, 期 1, 页码 H390-H397出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00662.2005
关键词
vascular smooth muscle cell; phosphatidylinositol 3-kinase; mitogen-activated protein kinase; 4E-binding protein 1; Src homology 2-containing inositol phosphatase 2; angiotensin II; peroxisome proliferator-activated receptor-gamma
The present study evaluated the effects of peroxisome proliferator-activated receptor (PPAR)-gamma 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 AT(1) receptor blocker valsartan or the AT(2) receptor blocker PD-123319, after pretreatment for 24 h with the PPAR-gamma activators 15-deoxy-Delta(12),(14)prostaglandin J(2) (15d-PGJ(2)) or rosiglitazone. Both 15d-PGJ(2) and rosiglitazone decreased ANG II-induced DNA synthesis. Rosiglitazone treatment increased nuclear PPAR-gamma expression and activity in VSMC. However, rosiglitazone did not alter expression of PPAR-alpha/beta, ERK 1/2, Akt, or ANG II receptors. 15d-PGJ(2) 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-gamma activation reduced ANG II-induced growth associated with inhibition of ERK 1/2, Akt, 4E-BP1, and SHIP2. Modulation of these pathways by PPAR-gamma activators may contribute to regression of vascular remodeling in hypertension.
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