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

American Journal of Physiology - Heart and Circulatory Physiology - Tập 290 Số 1 - Trang H390-H397 - 2006
Karim Benkirane1, Farhad Amiri, Quy N. Diep, Mohammed El Mabrouk, Ernesto L. Schiffrin
1Clinical Institute of Health Research Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1146/annurev.med.53.082901.104018

10.1046/j.1523-1755.2001.059003866.x

10.1126/science.296.5573.1655

Cooper ME. The role of the renin-angiotensin-aldosterone system in diabetes and its vascular complications. Am J Hypertens 17: 16S–20S, 2004.

Desvergne B and Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20: 649–688, 1999.

10.1161/01.CIR.0000016049.86468.23

10.1161/01.HYP.38.2.249

10.1161/01.HYP.0000060821.62417.35

10.1097/00004872-199401000-00001

10.1152/ajpheart.2001.281.1.H30

10.1126/science.275.5300.665

10.1016/S0021-9150(02)00014-X

10.1161/01.RES.0000060700.55247.7C

10.1097/00005344-200005000-00011

10.1016/S0014-5793(99)00624-9

10.1152/ajpheart.00040.2004

10.2337/diabetes.51.8.2387

10.1128/MCB.17.1.338

10.1016/S0895-7061(97)00164-7

10.1161/01.CIR.101.11.1311

10.1074/jbc.M301364200

10.1007/s001250050048

10.1161/01.HYP.0000051891.90321.12

10.1016/0895-7061(95)96214-5

10.1016/j.yjmcc.2004.05.015

10.2337/diacare.24.7.1226

10.1007/s00125-004-1636-8

10.1074/jbc.M106755200

10.1161/01.HYP.0000084370.74777.B6

10.1096/fasebj.9.9.7601337

10.1042/bj3600087

Sharma AM and Chetty VT. Obesity, hypertension and insulin resistance. Acta Diabetol 42, Suppl 1: S3–S8, 2005.

10.1161/01.RES.0000022200.71892.9F

10.1161/01.CIR.102.15.1834

10.1016/S0092-8674(00)81575-5

10.1097/00004872-199917070-00006

10.1161/01.HYP.38.1.56

10.1073/pnas.93.22.12490

10.1021/jm990554g

10.1161/01.ATV.19.1.73

Thông tin
Thông tin xuất bản

American Journal of Physiology - Heart and Circulatory Physiology

Tập 290 Số 1

H390-H397

Thông tin tác giả