The effects of sepsis on endothelium and clinical implications

TLDR

Sepsis, responsible for roughly 700,000 deaths annually in Europe, activates the endothelium, which amplifies the immune response, shifts to a procoagulant state, and can cause microvascular thrombosis, capillary leakage, hypotension, hypoxia, and organ damage. This review examines how endothelial dysfunction contributes to sepsis pathophysiology, focusing on leukocyte adhesion, reactive oxygen/nitrogen species, microRNAs, cytokines, microparticles, disseminated intravascular coagulation, permeability, apoptosis, and the diagnostic and therapeutic potential of endothelial markers. The authors synthesize evidence on endothelial mechanisms in sepsis—including leukocyte adhesion, ROS/RNS, microRNAs, cytokines, microparticle formation, DIC, permeability, and apoptosis—and evaluate endothelial markers as diagnostic and therapeutic targets.

Abstract

Abstract Sepsis accounts for nearly 700 000 deaths in Europe annually and is caused by an overwhelming host response to infection resulting in organ failure. The endothelium is an active contributor to sepsis and as such represents a major target for therapy. During sepsis, endothelial cells amplify the immune response and activate the coagulation system. They are both a target and source of inflammation and serve as a link between local and systemic immune responses. In response to cytokines produced by immune cells, the endothelium expresses adhesion molecules and produces vasoactive compounds, inflammatory cytokines, and chemoattractants, thus switching from an anticoagulant to procoagulant state. These responses contribute to local control of infection, but systemic activation can lead to microvascular thrombosis, capillary permeability, hypotension, tissue hypoxia, and ultimately tissue damage. This review focuses on the role of the endothelium in leucocyte adhesion and transmigration as well as production of reactive oxygen and nitrogen species, microRNAs and cytokines, formation of signalling microparticles, and disseminated intravascular coagulation. We also discuss alterations in endothelial permeability and apoptosis. Finally, we review the diagnostic potential of endothelial markers and endothelial pathways as therapeutic targets for this devastating disease.