FIGURE 3.

Graphical summary of possible mechanisms associated with how AMPK activation affects pulmonary vascular remodeling. Hypoxia/ROS/growth factors activate AMPK in ECs or VSMCs to promote or inhibit PH development. In pulmonary ECs, AMPK activation protects PH: (1) AMPK α1 activation in pulmonary ECs promotes Ca²⁺ influx to maintain endothelial barrier function, (2) pulmonary endothelial AMPK inhibits VCAM-1 expression to antagonize inflammatory cell infiltration, (3) AMPK activation in pulmonary ECs inhibits ROS production, promotes eNOS-NO bioactivity, and stabilizes ACE2 to increase Ang 1–7 expression. Pulmonary VSMC proliferation and contraction are thus regulated. In pulmonary VSMCs, AMPK α1 activation promotes autophagy-mediated cell survival; AMPK α2 activation inhibits cell apoptosis.