Endothelial cell injury: a crucial link in microcirculatory dysfunction associated with sepsis

BACKGROUND: Sepsis is a prevalent and severe condition, with microcirculation disruptions playing a crucial role in its progression. Endothelial cell (EC) injury is the primary factor behind microcirculatory issues. This review is to outline the pathomechanism, organ heterogeneity, biomarkers, and therapeutic implications of endothelial dysfunction in sepsis, offering references and insights for the clinical management of sepsis. METHODS: A systematic search of Web of Science and PubMed from inception to June 10, 2025, limited to English publications, was conducted. Two reviewers independently identified studies on EC injury in patients with septic microcirculatory dysfunction. Duplicate articles based on multiple search criteria were excluded. RESULTS: Fifty-nine articles, including cell, animal, and clinical studies, were included. These studies reported the effects of EC injury on the microcirculation in sepsis, including changes in vascular permeability, coagulation dysfunction, vasomotor regulation, and inflammatory responses. These pathways interact and ultimately lead to septic microcirculation disorders. CONCLUSION: Sepsis-induced endothelial dysfunction involves various interconnected mechanisms, which collectively compromise ECs and impede microcirculatory perfusion. Future research should enhance current understanding of endothelial injury mechanisms, develop synergistic multi-target strategies to disrupt this cycle, and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.