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

FEBS Letters

Sawada, Naoki¹  Itoh, Hiroshi¹  Yamahara, Kenichi¹  Miyashita, Kazutoshi¹  Yurugi-Kobayashi, Takami¹  Park, Kwijun¹  Nakao, Kazuwa¹  Fukunaga, Yasutomo¹  Sone, Masakatsu¹ 

[1] Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan

关键词: Adrenomedullin;    cAMP;    Akt;    Angiogenesis;    Re-endothelialization;    Vascular regeneration;    AM;    adrenomedullin;    PKA;    protein kinase A;    PI3K;    phosphatidylinositol 3-kinase;    HUVEC;    human umbilical vein endothelial cell;    NP;    natriuretic peptide;    PKA Inh. Peptide;    myristoylated protein kinase A inhibitor peptide sequence (14–22) cell-permeable;    FBS;    fetal bovine serum;   

DOI  :  10.1016/S0014-5793(03)00484-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown