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

• Published in: FEBS letters 2003-06, Vol.544 (1), p.86-92
• Main Authors: Miyashita, Kazutoshi, Itoh, Hiroshi, Sawada, Naoki, Fukunaga, Yasutomo, Sone, Masakatsu, Yamahara, Kenichi, Yurugi-Kobayashi, Takami, Park, Kwijun, Nakao, Kazuwa
• Format: Article
• Language: English
• Subjects: Adrenomedullin; Akt; AM, adrenomedullin; Angiogenesis; Animals; Biocompatible Materials - pharmacology; Blotting, Western; cAMP; Cell Division; Cell Movement; Cells, Cultured; Collagen - pharmacology; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Dose-Response Relationship, Drug; Drug Combinations; Endothelium - physiology; Endothelium, Vascular - cytology; Enzyme Activation; FBS, fetal bovine serum; Humans; HUVEC, human umbilical vein endothelial cell; Laminin - pharmacology; Mice; Neovascularization, Physiologic; NP, natriuretic peptide; Peptides - chemistry; Peptides - metabolism; Peptides - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; PI3K, phosphatidylinositol 3-kinase; PKA Inh. Peptide, myristoylated protein kinase A inhibitor peptide sequence (14–22) cell-permeable; PKA, protein kinase A; Protein Binding; Protein-Serine-Threonine Kinases; Proteoglycans - pharmacology; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Re-endothelialization; Regeneration; Time Factors; Vascular regeneration; Wound Healing
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)00484-8

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.