Expert Opin Ther Targets 2021 Oct 4. Endothelial dysfunction: a therapeutic target in bacterial sepsis? Jean-Louis Vincent 1, Can Ince 2, Peter Pickkers 3 Affiliations
1 Dept of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium.
2 Department of Intensive Care, Laboratory of Translational Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
3 Dept of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Abstract Introduction: Endothelial cells maintain vascular integrity, tone and patency and have important roles in hemostasis and inflammatory responses. Although some degree of endothelial dysfunction with increased vascular permeability may be necessary to control local infection, excessive dysfunction plays a central role in the pathogenesis of sepsis-related organ dysfunction and failure as it results in dysregulated inflammation, vascular leakage, and abnormal coagulation. The vascular endothelium has thus been proposed as a potential target for therapeutic intervention in patients with sepsis. Areas covered: Different mechanisms underlying sepsis-related dysfunction of the vascular endothelium will be discussed, including glycocalyx shedding, nitrosative stress, and coagulation factors. Potential therapeutic implications of each mechanism are mentioned. Expert opinion: Multiple targets to protect or restore endothelial function have been suggested, but endothelium-driven treatments remain a future potential at present. As some endothelial dysfunction and permeability may be necessary to remove infection and repair damaged tissue, targeting the endothelium may be a particular challenge. Ideally, therapies should be guided by biomarkers related to that specific pathway to ensure they are given only to patients most likely to respond. This enrichment based on biological plausibility and theragnostics will increase the likelihood of a beneficial response in an individual patient and enable more personalized treatment. Keywords: biomarker; coagulopathy; endothelial dysfunction; glycocalyx; multiple organ failure; nitric oxide; permeability; sepsis; vascular endothelium; vasoconstriction.