Effects of troglitazone and pioglitazone on cytokine-mediated endothelial cell proliferation in vitro.
We examined whether troglitazone and pioglitazone, antidiabetic thiazolidinediones, would directly induce endothelial cell proliferation or influence cytokine-driven proliferation in vitro. Monolayers of Balb/c mouse aortic endothelial cells were treated with troglitazone or pioglitazone in the absence of fetal bovine serum. Endothelial cells also were exposed to varying concentrations of basic fibroblast growth factor (bFGF) or insulin with or without either thiazolidinedione. After 48 h, 3-[4,5-dimethylthiozol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays were performed to quantitate endothelial cell proliferation by using the various treatment regimens. The data demonstrate that the antidiabetic thiazolidinediones troglitazone and pioglitazone negligibly affect direct endothelial cell proliferation in vitro. Furthermore, troglitazone and pioglitazone significantly inhibit bFGF-induced endothelial cell mitogenesis, whereas only high concentrations of troglitazone affect insulin-mediated proliferation.
Gralinski
M R
MR
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan, USA.
Rowse
P E
PE
Breider
M A
MA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000077205:Pioglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D016222:Fibroblast Growth Factor 2; D000077288:Troglitazone; D000077205:Pioglitazone