Table 1.

Mechanisms involved in endothelial damage in sepsis.

Mechanism	Pathway
Endothelial apoptosis	LPS induces cell death. NETs produce cell death through the direct toxicity of histones and proteases.
Endothelial denudation	LPS provokes endothelial cell detachment from basal membrane/internal elastic lamina.
Endothelial sensitization	ANGPT-2 sensitizes endothelial cells to inflammatory cytokines and promotes leakage.
Endothelial permeability	Inflammatory cytokines increase the EC permeability.
Alteration of endothelial histology	LPS can induce nuclear vacuolization, cytoplasmic swelling and protrusion and cytoplasmic fragmentation.
Suppression of endothelial anticoagulant receptors	Inflammatory cytokines downregulate EPCR and thrombomodulin.
Catecholamines-induced injury	Elevated levels of noradrenaline cause glycocalyx disruption.
Reduced sensitivity to catecholamines	LPS reduces vessel relaxation mediated by ACh.
Joint proteins internalization	Inflammation induces VE-cadherin dislocation.

LPS, lipopolysaccharide; NET, neutrophil extracellular trap; ACh, acetylcholine; ANGPT-2, angiopoietin-2; EPCR, endothelial protein C receptor and ECs, endothelial cells.