Pioglitazone reduces monocyte adhesion to vascular endothelium under flow by modulating RhoA GTPase and focal adhesion kinase.
Thiazolidinediones (TZDs), potent peroxisome proliferator-activated receptor gamma 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 mumol/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.
Toriumi
Yasutoshi
Y
Department of Vascular Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima Bldg. D-256, Bunkyo-ku, 113-8519 Tokyo, Japan.
Hiraoka
Megumi
M
Watanabe
Mamoru
M
Yoshida
Masayuki
M
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D000077205:Pioglitazone; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D016023:Integrins; D045162:Thiazolidinediones; D015237:Dinoprost; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020558:GTP Phosphohydrolases; D020742:rhoA GTP-Binding Protein; D000077205:Pioglitazone