Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.

Purpose of review: Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies. We also describe studies of metabolic interventions that aim to inhibit ALI/ARDS and/or promote post-sepsis vascular repair, including those that target endothelial cell metabolites, endothelial cell metabolic signaling pathways, and endothelial cell metabolism.

Recent findings: Endothelial cells are integral to both the injury and repair phases of ALI/ARDS. During the injury phase of ALI/ARDS, lung endothelial cell survival decreases, and lung endothelial cell-to-endothelial cell (EC-EC) junctions are weakened. During the repair phase after sepsis-induced lung injury, lung endothelial cell proliferation and lung EC-EC junction reannealing occur. These crucial aspects of ALI/ARDS and post-sepsis vascular repair, that is, endothelial cell viability, growth, and junction integrity, are controlled by a myriad of metabolites and metabolic signaling pathways in endothelial cells.

Summary: Metabolic signaling pathways in endothelial cells represent a novel class of putative targets for the prevention and treatment of sepsis-induced inflammatory lung injury. Therapies that target metabolic signaling in endothelial cells are currently being explored as potential treatments for sepsis-induced inflammatory lung injury.