Hyaluronan and angiogenesis.

Remodelling tissues, in both normal and pathological situations, show a greatly increased synthesis and turnover of hyaluronan. An essential part of these processes is new blood vessel formation. Whereas native hyaluronan has been reported to inhibit angiogenesis in vivo, partial degradation products (4-25 disaccharide units) have been found to stimulate angiogenesis in several in vivo systems. Examination of the effect of hyaluronan and its oligosaccharides on cultured cells suggests that these effects are due to the direct action of hyaluronan on endothelial cells. Native HA inhibits endothelial cell proliferation and disrupts cell-cell/cell-substrate interactions at physiological concentration. Angiogenic oligosaccharides induce both endothelial proliferation and migration, possibly via a receptor-mediated mechanism. Thus the metabolic state of hyaluronan could have profound effects on tissue neovascularization.