Vascular endothelial growth factor promotes cell-cycle transition from G0 to G1 phase in subcultured endothelial cells of diabetic rat thoracic aorta.

Vascular endothelial growth factor (VEGF) has been claimed to be a major positive regulator of angiogenesis in diabetic retinopathy and atherosclerosis. Diabetic state-induced alteration of the phenotypes and the influence of 12-h pretreatment with VEGF were examined after a further 12-h treatment with only 1% fetal bovine serum in subcultured endothelial cells (EC) derived from rat thoracic aorta. By flow cytometric cell cycle analysis, VEGF showed quite different transition patterns from those of platelet-derived growth factor (PDGF) in 5-day (at the progression phase) cultured normal rat EC even though VEGF belongs to the PDGF family. VEGF promoted cell cycle transition from the G0 to the G1 phase at 3 ng/ml, but at 30 ng/ml, VEGF weakly inhibited it compared with the effect of PDGF. The streptozotocin-diabetic state promoted cell cycle transition of EC from the G0 to the G1 phase. The promotion by the low concentration of VEGF was observed even at the point of 35-day culture (angiogenic EC at the competence phase in normal state). The diabetic state enhanced EC proliferation rather than tube formation, and the tube formation was scarce. The promotion of cell cycle transition by VEGF may aggravate furthermore diabetic angiopathy due to the leaky constitution of blood vessels.