Amp-Kinase (Ampk) Activation Attenuates Lps-Induced Lung Microvascular Endothelial Injury

AMPK is a molecular sensor for detection and mediation of cellular adaptations to vascular disruptive stimuli. We have shown previously that AMPKα1 stimulation by endothelial disruptive stimuli enhances repair of injured capillaries. In this study, we hypothesized that bacterial derived endotoxin lipopolysaccharide‐induced activation of AMPK limits vascular injury in the pulmonary capillary circulation. AMPK activity studies reveal that LPS induces a rapid increase in kinase activity that remains elevated over time. Western blot analysis and PCR indicate expression of the AMPKα1 subunit is enhanced by LPS in pulmonary microvascular cells (PMVECs) in culture. These data were confirmed by immunohistology in the lungs of LPS treated rats. Moreover, inhibition of AMPK increased the permeability and decreased the resistance of LPS treated PMVECs in culture and exacerbated LPS‐induced vascular injury in the isolated rat lung. Taken together these data identify AMPK as a barrier protective mechanism in the LPS‐treated lung. Supported by HL102296 and HL 110803.