AMP-Activated Protein Kinase α1 in Macrophages Promotes Collateral Remodeling and Arteriogenesis in Mice In Vivo

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—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...