Adrenomedullin provokes endothelial Akt activation and promotes vascular regeneration both in vitro and in vivo

Kazutoshi Miyashita, Hiroshi Itoh, Naoki Sawada, Yasutomo Fukunaga, Masakatsu Sone, Kenichi Yamahara, Takami Yurugi-Kobayashi, Kwijun Park, Kazuwa Nakao

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

We previously reported that adrenomedullin (AM), a vasodilating hormone secreted from blood vessels, promotes proliferation and migration of human umbilical vein endothelial cells (HUVECs). In this study, we examined the ability of AM to promote vascular regeneration. AM increased the phosphorylation of Akt in HUVECs and the effect was inhibited by the AM antagonists and the inhibitors for protein kinase A (PKA) or phosphatidylinositol 3-kinase (PI3K). AM promoted re-endothelialization in vitro of wounded monolayer of HUVECs and neo-vascularization in vivo in murine gel plugs. These effects were also inhibited by the AM antagonists and the inhibitors for PKA or PI3K. The findings suggest that AM plays significant roles in vascular regeneration, associated with PKA- and PI3K-dependent activation of Akt in endothelial cells, and possesses therapeutic potential for vascular injury and tissue ischemia.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalFEBS Letters
Volume544
Issue number1-3
DOIs
Publication statusPublished - 2003 Jun 5

Keywords

  • Adrenomedullin
  • Akt
  • Angiogenesis
  • Re-endothelialization
  • Vascular regeneration
  • cAMP

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Miyashita, K., Itoh, H., Sawada, N., Fukunaga, Y., Sone, M., Yamahara, K., Yurugi-Kobayashi, T., Park, K., & Nakao, K. (2003). Adrenomedullin provokes endothelial Akt activation and promotes vascular regeneration both in vitro and in vivo. FEBS Letters, 544(1-3), 86-92. https://doi.org/10.1016/S0014-5793(03)00484-8