Ikuko Kimura1, Ritsu Honda1, Hisashi Okai1
and Motonori Okabe2
1Departmentﾊof Chemical Pharmacology, Faculty of Pharmaceutical
Sciences and 2Department of Anatomy 2, Faculty of Medicine,
Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194,
Japan
Abstract: 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ﾊng/ml, but at 30ﾊ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.
Keywords: Vascular endothelial growth factor (VEGF), Streptozotocin-diabetic
rat, Subcultured endothelial cell (thoracic aorta), Cell cycle, Flow cytometry