Sepsis-Induced Endothelial Barrier Dysfunction: Mechanisms, Pathology, and Therapeutic Advances

Sepsis is a life-threatening disease characterized by systemic inflammation and endothelial barrier dysfunction, leading to multiorgan failure and high mortality. This review provides a comprehensive overview of the pathological mechanisms underlying sepsis-induced endothelial dysfunction, focusing on glycocalyx degradation, endothelial cell death, increased vascular permeability, and coagulopathy. During sepsis, the endothelial glycocalyx (EG) is disrupted, leading to increased vascular permeability and impaired microcirculation. Endothelial cells undergo various forms of cell death, including apoptosis, pyroptosis, ferroptosis, and autophagy, which are driven by inflammation and oxidative stress. These processes are further complicated by the activation of coagulation pathways and the formation of intravascular thrombi. The interaction between endothelial cells and immune cells amplifies the inflammatory response, contributing to the persistence of systemic inflammation. We also discuss emerging therapeutic strategies aimed at protecting endothelial cells, modulating inflammation, and improving coagulation function, including glycocalyx protectants, anti-inflammatory agents, anticoagulants, and endothelial repair mechanisms. Future research should focus on translating these therapeutic approaches into clinical practice to improve outcomes in patients with sepsis.