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

Department of Medicine and Clinical Science, Kyoto University, Kioto, Kyōto, Japan
FEBS Letters (Impact Factor: 3.34). 07/2003; 544(1-3):86-92. DOI: 10.1016/S1567-5688(03)90843-9
Source: PubMed

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.

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    Inflammation and Regeneration 01/2008; 28(2):105-110. DOI:10.2492/inflammregen.28.105
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    ABSTRACT: To investigate the roles of an adrenomedullin receptor antagonist (adrenomedullin22-52) on high-glucose-induced human retinal endothelial cell (HREC) in vitro cell biology. HRECs were cultured with different concentrations of glucose and adrenomedullin22-52. The proliferation of HRECs was evaluated by a cell counting kit-8 assay. Cell migration was assessed by scratch wound assay, and cell sprouting was detected by tube formation assay. The mRNA levels of adrenomedullin (ADM), vascular endothelial growth factor (VEGF), ADAMTS-1, and TSP-1 were measured by reverse-transcription polymerase chain reaction (RT-PCR). The VEGF and phosphatidylinositol 3' kinase (PI3K) pathway protein expression levels were assessed by western blot analysis. Compared with 5 mM normal glucose treatment, 30 mM glucose significantly promoted the migration of HRECs, which was attenuated by 1 μg/ml adrenomedullin22-52. The proliferation of HRECs was also suppressed by 1 μg/ml adrenomedullin22-52. Furthermore, compared with other groups, 5 μg/ml of adrenomedullin22-52 was shown to suppress high-glucose-induced tube formation of HRECs. With adrenomedullin22-52 treatment, the mRNA level of ADAMTS-1 was significantly increased. Moreover, western blot and RT-PCR analyses showed that HRECs treated with 30 mM glucose exhibited increased VEGF and PI3K pathway protein levels, while the expression levels were suppressed by 5 μg/ml of adrenomedullin22-52. Our study indicated that adrenomedullin22-52 mediated the migration, proliferation and tube formation after HRECs were exposed to high levels of glucose, which may be related to its ability to affect the expression of VEGF through the PI3K pathway.
    Molecular vision 03/2014; 20:259-69. · 2.25 Impact Factor

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