Endothelial barrier dysfunction in systemic inflammation is mediated by soluble VE-cadherin interfering VE-PTP signaling.

ABSTRACT: Breakdown of endothelial barrier integrity determines organ dysfunction and outcome of patients with sepsis. Increased levels of soluble vascular endothelial (VE)-cadherin fragments (sVE-cadherin) have previously been linked with inflammation-induced loss of endothelial barrier function. We provide evidence for a causative role of sVE-cadherin to induce loss of endothelial barrier function. In patients with sepsis, sVE-cadherin levels were associated with organ dysfunction and the need for volume resuscitation. Similarly, LPS-induced systemic inflammation in rats with microvascular dysfunction was paralleled by augmented sVE-cadherin levels. Newly generated recombinant human sVE-cadherin (extracellular domains EC1-5) induced loss of endothelial barrier function in both human microvascular

SUBMITTER: Knop JL 

PROVIDER: S-EPMC10563049 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature