Pioglitazone reduces monocyte adhesion to vascular endothelium under flow by modulating RhoA GTPase and focal adhesion kinase

FEBS Letters

Watanabe, Mamoru²  Yoshida, Masayuki¹  Hiraoka, Megumi¹  Toriumi, Yasutoshi¹ 

[1] Department of Vascular Medicine, Medical Biochemistry, Tokyo Medical and Dental University, 1-5-45, Yushima Bldg. D-256, Bunkyo-ku, Tokyo 113-8519, Japan;Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan

关键词: Thiazolidinedione;    Monocyte adhesion;    Cytoskeletal organization;    Atherosclerosis;   

DOI  :  10.1016/S0014-5793(03)01040-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Thiazolidinediones (TZDs), potent peroxisome proliferator-activated receptor γ ligands, have been shown to improve endothelial function in vascular diseases. We investigated the effects of pioglitazone, a TZD, on monocyte–endothelial interaction under flow and found that pretreatment (20 μmol/l, 48 h) significantly reduced U937 adhesion to human umbilical vein endothelial cells. Integrin expression was not altered, however, the activation of RhoA GTPase was significantly reduced after treatment. Further, pioglitazone treatment significantly reduced phosphorylation of focal adhesion kinase (FAK) at 925Y, but not at 397Y, suggesting a specific role in FAK-dependent signaling. These results indicate a novel anti-inflammatory role for this compound.

【 授权许可】

Unknown