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Angiogenesis can be stimulated or repressed in vivo by a change in GM3:GD3 ganglioside ratio
M Ziche1, L Morbidelli, G Alessandri
1Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Background:
We had previously observed that rabbit cornea stimulated by an angiogenic factor 1) became richer in total gangliosides and 2) reduced the GM3:GD3 ganglioside ratio. Moreover, experimentally induced global enrichment of corneal gangliosides favors angiogenesis.
Experimental Design:
The objective of this work was to explain the possible relationship between angiogenic response and changes in the GM3:GD3 ratios observed in vivo. Cornea was utilized because it is avascular and transparent; i.e., the onset of opacity permitted exclusion of angiogenesis produced by a generic inflammatory response. Prostaglandin E1 or basic fibroblast growth factor were applied as angiogenesis triggers. Angiogenesis in vivo and mobilization and growth of microvascular endothelium in vitro were taken as parameters to indicate whether differences in GM3:GD3 ratios could modify the extent of the angiogenic response.
Results:
In vivo angiogenesis, whether prostaglandin E1 or basic fibroblast growth factor induced, was repressed by GM3 and enhanced by GD3 or GM1 enrichment of the cornea. In vitro growth and motility of microvascular endothelium were reduced by GM3 addition to the medium and returned to normal levels by addition of GD3.
Conclusions:
Formation of new vessels induced by two different angiogenic factors could be stimulated or repressed in the cornea by reduction or enhancement of the GM3:GD3 ratio of tissue gangliosides. Changes in the relative proportion of molecules normally present in adult tissues, like prostaglandin E1, basic fibroblast growth factor, GM3, GD3, were sufficient to modulate or even block angiogenesis.