High mobility group box 1 complexed with heparin induced angiogenesis in a matrigel plug assay

Hidenori Wake, Shuji Mori, Keyue Liu, Hideo K. Takahashi, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Angiogenesis involves complex processes mediated by several factors and is associated with inflammation and wound healing. High mobility group box 1 (HMGB1) is released from necrotic cells as well as macrophages and plays proinflammatory roles. In the present study, we examined whether HMGB1 would exhibit angiogenic activity in a matrigel plug assay in mice. HMGB1 in combination with heparin strongly induced angiogenesis, whereas neither HMGB1 nor heparin alone showed such angiogenic activity. The heparin-dependent induction of angiogenesis by HMGB1 was accompanied by increases in the expression of tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor-A120 (VEGF-A120). It is likely that the dependence of the angiogenic activity of HMGB1 on heparin was due to the efficiency of the diffusion of the HMGBl-heparin complex from matrigel to the surrounding areas. VEGF-A165 possessing a heparin-binding domain showed a pattern of heparin-dependent angiogenic activity similar to that of HMGB1. The presence of heparin also inhibited the degradation of HMGB1 by plasmin in wtro. Taken together, these results suggested that HMGB1 in complex with heparin possesses remarkable angiogenic activity, probably through the induction of TNF-α and VEGF-A120.

Original languageEnglish
Pages (from-to)249-262
Number of pages14
JournalActa Medica Okayama
Issue number5
Publication statusPublished - Nov 2009


  • Angiogenesis
  • HMGB1
  • Heparin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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