Jpn. J. Pharmacol. 83 (1), 47-55 (2000)

Vascular Endothelial Growth Factor Promotes Cell-Cycle Transition From G0 to G1 Phase in Subcultured Endothelial Cells of Diabetic Rat Thoracic Aorta

Ikuko Kimura1, Ritsu Honda1, Hisashi Okai1 and Motonori Okabe2

1Department╩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╩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.

Keywords: Vascular endothelial growth factor (VEGF), Streptozotocin-diabetic rat, Subcultured endothelial cell (thoracic aorta), Cell cycle, Flow cytometry

Copyrightę The Japanese Pharmacological Society 2000

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