Hyaluronic acid-like substance from mouse ovaries with angiogenic activity

Glycosaminoglycans prepared from extracts of non-luteal mouse ovaries (JCL-ICR strain) were assayed for neovascularization by implanting Elvax films, impregnated with test samples, on the lateral wall of the sheath of m. rectus abdominis in adult mice of the same strain. Neovascularization occurred in a dose-dependent manner. When purified by chromatography on Dowex 1-x2 and DEAE Sephadex columns, fractions eluted with 0.5 M NaCl showed strong neovascularizing activity. On further purification by high performance liquid chromatography using TSK gel DEAE 2 SW column, the fraction with a retention time nearly coincident with that of hyaluronic acid possessed high neovascularizing activity. The activity of this fraction was markedly reduced when treated with streptococcal hyaluronidase. The present results suggest that glycosaminoglycans, especially a hyaluronic acid-like substance, are involved in ovarian neovascularization.