Expert opinion on therapeutic targets | 2021
Endothelial dysfunction: a therapeutic target in bacterial sepsis?
Abstract
INTRODUCTION\nEndothelial 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.\n\n\nAREAS COVERED\nDifferent 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.\n\n\nEXPERT OPINION\nMultiple 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.