Succinate metabolism and membrane reorganization drives the endotheliopathy and coagulopathy of traumatic hemorrhage.

ABSTRACT: Acute hemorrhage commonly leads to coagulopathy and organ dysfunction or failure. Recent evidence suggests that damage to the endothelial glycocalyx contributes to these adverse outcomes. The physiological events mediating acute glycocalyx shedding are undefined, however. Here, we show that succinate accumulation within endothelial cells drives glycocalyx degradation through a membrane reorganization-mediated mechanism. We investigated this mechanism in a cultured endothelial cell hypoxia-reoxygenation model, in a rat model of hemorrhage, and in trauma patient plasma samples. We found that succinate metabolism by succinate dehydrogenase mediates glycocalyx damage through lipid oxidation and phospholipase A2-mediated membrane reorganization, promoting the interaction of matrix metalloprotei

SUBMITTER: Abdullah S 

PROVIDER: S-EPMC10266735 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature