TY - JOUR
T1 - Adrenomedullin provokes endothelial Akt activation and promotes vascular regeneration both in vitro and in vivo
AU - Miyashita, Kazutoshi
AU - Itoh, Hiroshi
AU - Sawada, Naoki
AU - Fukunaga, Yasutomo
AU - Sone, Masakatsu
AU - Yamahara, Kenichi
AU - Yurugi-Kobayashi, Takami
AU - Park, Kwijun
AU - Nakao, Kazuwa
PY - 2003/6/5
Y1 - 2003/6/5
N2 - 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.
AB - 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.
KW - Adrenomedullin
KW - Akt
KW - Angiogenesis
KW - Re-endothelialization
KW - Vascular regeneration
KW - cAMP
UR - http://www.scopus.com/inward/record.url?scp=0038018585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038018585&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(03)00484-8
DO - 10.1016/S0014-5793(03)00484-8
M3 - Article
C2 - 12782295
AN - SCOPUS:0038018585
SN - 0014-5793
VL - 544
SP - 86
EP - 92
JO - FEBS Letters
JF - FEBS Letters
IS - 1-3
ER -