| First Author | Zhu H | Year | 2016 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 36 |
| Issue | 9 | Pages | 1868-78 |
| PubMed ID | 27444205 | Mgi Jnum | J:246308 |
| Mgi Id | MGI:5921739 | Doi | 10.1161/ATVBAHA.116.307743 |
| Citation | Zhu H, et al. (2016) AMP-Activated Protein Kinase alpha1 in Macrophages Promotes Collateral Remodeling and Arteriogenesis in Mice In Vivo. Arterioscler Thromb Vasc Biol 36(9):1868-78 |
| abstractText | 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 AND RESULTS: AMPKalpha1, AMPKalpha2 knockout and wild-type littermates underwent femoral artery ligation. Collateral arteriogenesis was monitored in wild-type, global AMPKalpha1 knockout, or macrophage-specific AMPKalpha1 knockout mice, with or without hindlimb ligation. Compared with wild-type mice with ligation, global AMPKalpha1 knockout mice displayed significant reduction in blood flow recovery and impaired remodeling of collateral arterioles. Similar impairments were observed in macrophage-specific AMPK alpha1 knockout mice after hindlimb ligation. Mechanistically, we found that AMPKalpha1 promotes the production of growth factors, such as transforming growth factor beta, by directly phosphorylating the inhibitor of nuclear factor kappaB kinase alpha, resulting in an nuclear factor kappaB-dependent production of growth factors CONCLUSIONS: Our findings suggest a novel role for macrophage AMPKalpha1 in arteriogenesis and collateral remodeling and indicate that AMPKalpha1 activation might be beneficial for recovery from occlusive vascular disorders. |
