ORIGINAL ARTICLES   

International Angiology 2000 March;19(1):26-34

Copyright © 2001 EDIZIONI MINERVA MEDICA

lingua: Inglese

Vascular endothelial growth-factor- and platelet-derived growth factor-angiogenesis depressed but fetal bovine serum-angiogenesis enhanced choroidal tissue cultures of streptozotocin-diabetic wistar and GK rats

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.