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Official Journal of the , the International Union of Phlebology and the
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 0,899
Online ISSN 1827-1839
Kimura I. *, Yanagita S., Kobayshi S. *, Fukuta M., Okabe M. **
From the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
* Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
** Department of Anatomy, Faculty of Medical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan
Background: Diabetic state-induced alterations of angiogenic activity of vascular endothelial growth factor and platelet-derived growth factor were compared with that of fetal bovine serum (FBS) in the cultured choroidal explants of streptozotocin (STZ)-diabetic Wistar and diabetic GK rats.
Methods: Choroidal explants (0.04-1.0 mm2) were isolated from rat eyeballs and cultured in fibrin gels with FBS-Dulbecco’s modified Eagle’s medium (0.5 mL) containing antibiotics and 300 μg/mL ε-amino caproic acid in the presence of recombinant mouse vascular endothelial growth factor and recombinant human platelet-derived growth factor BB at 37°C under 5% CO2 and 95% air. Microvessels newly budded from these choroidal explants were photographed. The number and length of all microvessels per choroidal explant were counted and measured as indices of angiogenesis in vitro.
Results: Fetal bovine serum (5-10%) enhanced both angiogenic indices in the explants of STZ-diabetic Wistar and GK rats. The actions of the serum on both angiogenic indices in both diabetic rats were greater than those in age-matched normal rats. Vascular endothelial growth factor (3-30 ng/mL) with 1% fetal bovine serum increased the angiogenic indices in diabetic choroids, but was less pronounced than in normal choroids. The action of platelet derived growth factor (2.5 ng/mL) on angiogenesis was also less in diabetic choroids.
Conclusions: Results suggest that the diabetic state may down-regulate the receptors for vascular endothelial and platelet-derived growth factors and/or desensitize their post-receptor signaling in the vascular endothelial cells of choroids, being inexplicable for the enhanced actions of fetal bovine serum on angiogenesis in diabetic choroids.