Gangliosides promote the angiogenic response.
Formation of new capillaries was induced in rabbit corneas by optimal doses of prostaglandin E1 (PGE1) or basic fibroblastic growth factor. Suboptimal doses of either of these angiogenesis inducers were unable to elicit corneal angiogenesis. However, the addition of gangliosides (GM1 or GT1b) to the insufficient dose of the angiogenic inducer, not only promoted neovascularization but strongly enhanced the number and growth rate of the newly formed capillaries as compared with the effect of an optimal dose of the angiogenesis inducer alone. Removal of the ganglioside stimulation led to the disappearance of the newly formed capillaries. Re-establishment of the ganglioside stimulation renewed the appearance of a conspicuous vascular network. Removal of sialic acid from the ganglioside molecule nullified its stimulatory effect on angiogenesis. GMI or GT1b or sialic acid were not angiogenic by themselves. Corneas ready to be invaded by newly formed capillaries induced by an optimal dose of an angiogenesis factor such as PGE1 had a ganglioside content about twice that of unstimulated corneas. The results are interpreted to indicate that ganglioside molecules influence capillary formation not as angiogenesis inducers but as promoters of vessel morphogenesis. The data support the hypothesis that in vivo the level of gangliosides in the tissue milieu could influence the evolution of pathologic processes in which new formation of capillaries is a critical event.
Ziche
M
M
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Alessandri
G
G
Gullino
P M
PM
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000032:analysis; D003315:Cornea / Q000032:analysis / Q000098:blood supply / Q000502:physiology; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D005732:Gangliosides / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011817:Rabbits; D012794:Sialic Acids / Q000494:pharmacology
D005353:Fibronectins; D005732:Gangliosides; D012794:Sialic Acids; D005346:Fibroblast Growth Factors; D000527:Alprostadil