Effect of thiazolidinedione on the proliferation of bovine retinal endothelial cells stimulated by vascular endothelial cell growth factor

Purpose: To investigate the effect of troglitazone, an antidiabetic drug, on the cytosolic Ca2+ concentrations ([Ca2+](i)) and the cell cycles of bovine retinal endothelial cells (RECs) stimulated with vascular endothelial growth factor (VEGF). Methods: The changes in [Ca2+](i) were monitored using microfluorometry with Fura-2. The phase of the cell cycle was examined by an immunocytochemical analysis using monoclonal antibodies against cell cycle-specific nuclear antigens. Results: In the presence of extracellular Ca2+, VEGF-induced transient [Ca2+](i) elevation followed by continuous steady-state elevation resulted in cell cycle progression in RECs. The removal of extracellular Ca2+ inhibited the continuous component, but transient [Ca2+](i) elevation was still observed. These results are compatible with the hypothesis that a continuous steady-state elevation of [Ca2+](i) may be mediated mainly through the influx of extracellular Ca2+. Pretreatment with 10 mu M troglitazone prevented the transient and continuous steady-state elevation of [Ca2+](i), resulting in an inhibition of the cell cycle in RECs stimulated with VEGF. Conclusions: These data suggest that troglitazone inhibits VEGF-induced cell cycle progression through the inhibition of [Ca2+](i) in RECs.