Application of angiogenic oligosaccharides of hyaluronan increases blood vessel numbers in rat skin.

Angiogenic oligosaccharides of hyaluronan were applied to the backs of young, adult male rats and the number of blood vessels, within a depth of 136 microns beneath the base of the epidermis, were evaluated. Application of hyaluronan oligosaccharides significantly increased the mean number of blood vessels/mm skin length in six of 11 treated rats when compared with controls. Application of radiolabeled hyaluronan oligosaccharides to skin of one rat demonstrated a penetration to a depth of approximately 800 microns, suggesting that the blood vessels beneath the epidermis would be exposed to the hyaluronan. Hyaluronan has previously been shown to stimulate endothelial cell proliferation; we demonstrate here that these hyaluronan oligosaccharides also specifically stimulate endothelial cell migration. This action of hyaluronan oligosaccharides may prove useful in retarding blood vessel paucity and degeneration observed during the ageing process and following radiotherapy.