AMP-Activated Protein Kinase α1 in Macrophages Promotes Collateral Remodeling and Arteriogenesis in Mice In Vivo.
Arterioscler Thromb Vasc Biol
; 36(9): 1868-78, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27444205
ABSTRACT
OBJECTIVE:
AMP-activated protein kinase (AMPK), an energy and redox sensor, is activated in response to various cellular stresses, including hypoxia, nutrient deprivation, oxidative stress, and fluid shear stress at the site of vessel blockade. The activation of AMPK is involved in angiogenesis. However, it is unknown whether AMPK can influence arteriogenesis. Here, we demonstrate the contribution of macrophage AMPK to arteriogenesis and collateral remodeling and their underlying mechanisms in well-characterized in vivo and in vitro models. APPROACH ANDRESULTS:
AMPKα1, AMPKα2 knockout and wild-type littermates underwent femoral artery ligation. Collateral arteriogenesis was monitored in wild-type, global AMPKα1 knockout, or macrophage-specific AMPKα1 knockout mice, with or without hindlimb ligation. Compared with wild-type mice with ligation, global AMPKα1 knockout mice displayed significant reduction in blood flow recovery and impaired remodeling of collateral arterioles. Similar impairments were observed in macrophage-specific AMPK α1 knockout mice after hindlimb ligation. Mechanistically, we found that AMPKα1 promotes the production of growth factors, such as transforming growth factor ß, by directly phosphorylating the inhibitor of nuclear factor κB kinase alpha, resulting in an nuclear factor κB-dependent production of growth factorsCONCLUSIONS:
Our findings suggest a novel role for macrophage AMPKα1 in arteriogenesis and collateral remodeling and indicate that AMPKα1 activation might be beneficial for recovery from occlusive vascular disorders.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Circulação Colateral
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Músculo Esquelético
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Neovascularização Fisiológica
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Proteínas Quinases Ativadas por AMP
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Remodelação Vascular
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Isquemia
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Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article