Endothelial dysfunction: Pathophysiology and therapeutic targets for sepsis-induced multiple organ dysfunction syndrome

Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients. • Sepsis and septic shock are serious conditions with high mortality rates and a major global health concern. • Endothelial dysfunction is a key factor in the progression from sepsis to severe multiorgan dysfunction syndrome. • Endothelial dysfunction can be attributed to glycocalyx damage, dysregulated NO metabolism, adhesion and inflammation. • Glycocalyx damage, dysregulated NO metabolism, adhesion, and inflammation cause endothelial dysfunction. • Potential therapeutic small molecules modulate endothelial function to improve sepsis and multi-organ damage.