Rosiglitazone inhibits endothelial proliferation and angiogenesis.
Rosiglitazone, an insulin sensitizer, is known to offer beneficial effects in retarding atherosclerotic vascular diseases. Since proliferation and angiogenesis are involved in initiation and plaque instability, two critical steps in the cardiovascular events, this study was designed to evaluate the mechanisms of rosiglitazone on endothelial proliferation and angiogenesis. Rosiglitazone-treated human umbilical vein endothelial cells were analyzed for growth rate by use of cell number counting, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay as well as 3H-thymidine incorporation. Cell cycle analysis was detected by flow cytometry and cell cycle-related proteins were measured by Western blot. Effects of rosiglitazone on angiogenesis were assessed by vascular endothelial growth factor (VEGF)-induced tube formation and wound-healing migration. Furthermore, effects of rosiglitazone on actin stress fiber were observed under confocal microscopy. Our data showed that rosiglitazone inhibits endothelial proliferation in a dose-dependent manner. Rosiglitazone caused endothelial arrest at G1 phase via affecting several cell cycle-related proteins that led to attenuate phosphorylation of retinoblastoma protein. Rosiglitazone markedly decreased VEGF-induced tube formation and endothelial cell migration, which might be explained by a disorganization of the actin cytoskeleton. Our data suggest that both anti-proliferative and anti-angiogenic activities in endothelial cells might account for the greater than expected beneficial effects of rosiglitazone for the treatment and prevention of atherosclerosis.
Sheu
Wayne Huey-Herng
WH
Division of Endocrinology and Metabolism, Department of Education and Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Ou
Hsiu-Chung
HC
Chou
Fen-Pi
FP
Lin
Tsung-Min
TM
Yang
Ching-Hwa
CH
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014471:Umbilical Veins; D014665:Vasodilator Agents / Q000494:pharmacology*
D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D013936:Thymidine