Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis

• DOI: 10.1126/sciadv.abm8965
• Publication Date: 2022-04-27T17:58:00Z
• Authors: Kun Yang; Min Fan; Xiaohui Wang; Jingjing Xu; Yana Wang; P. Spencer Gill; Tuanzhu Ha; Li Liu; Jennifer V. Hall; David L. Williams; Chuanfu Li
• Keywords: Vascular permeability; VE-cadherin; Pathophysiology

Circulating lactate levels are a critical biomarker for sepsis and positively correlated with sepsis-associated mortality. We investigated whether plays biological role in causing endothelial barrier dysfunction sepsis. showed that causes vascular permeability worsens organ CLP Mechanistically, induces ERK-dependent activation of calpain1/2 VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis cells. In addition, we found ERK2 interacts stabilizes complex resting Lactate-induced phosphorylation promotes disassociation from VE-cadherin. vivo suppression production or genetic depletion receptor GPR81 mitigates multiple injury improves survival outcome polymicrobial Our study reveals metabolic cross-talk between glycolysis-derived endothelium pathophysiology