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Recently, the research team led by Academician Jiang Jianxin of the Army Medical University, Researcher Zeng Ling, and Professor Wang Zhen systematically discussed the molecular mechanisms, pathological processes, and latest clinical treatment progress of vascular endothelial barrier dysfunction induced by sepsis from the perspective of vascular endothelial cells. This provided new precise intervention ideas for sepsis and septic shock. The paper was published in Research under the title "Sepsis-Induced Endothelial Barrier Dysfunction: Mechanisms, Pathology, and Therapeutic Advances". Citation: Rui Wang, Qiuju Han, Jiangbo Fan, Zhe Xu, Wenyi Liu, Di Liu, You Li, Juan Du, Jianhui Sun, Huacai Zhang, et al. Sepsis-Induced Endothelial Barrier Dysfunction: Mechanisms, Pathology, and Therapeutic Advances. Research. 2025; 8: 0997. DOI: 10.34133/research.0997 Research Background
Sepsis, as a systemic inflammatory response syndrome triggered by infection and life-threatening, has a high mortality rate (the mortality rate of septic shock is 40% - 50%). This issue has long plagued clinical practice. The core pathological process is the "collapse" of the vascular endothelial barrier, which leads to vascular leakage and abnormal coagulation function and immune dysfunction, ultimately resulting in multiple organ failure. The current treatment strategies mainly focus on pathogen clearance and organ function support, but lack systematic and targeted intervention plans for vascular endothelial barrier damage.
Research progress
I. The core mechanism of endothelial barrier dysfunction in sepsis
Firstly, elevated lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) in the plasma during sepsis can activate endothelial heparanase, causing the detachment of the endothelial glycocalyx (EG), increasing the permeability of the vessel to large molecules, and exposing adhesion molecules such as E-selectin and ICAM-1, triggering granulocyte adhesion and severe inflammatory reactions that further aggravate endothelial glycocalyx damage, leading to the failure of the "first line of defense" of the vascular barrier. Secondly, in the sepsis state, intense inflammatory responses and oxidative stress will induce various programmed cell deaths in endothelial cells, including apoptosis, pyroptosis, ferroptosis, and autophagy. The simultaneous occurrence of these death modes exacerbates the destruction of the endothelial barrier. Finally, neutrophil elastase, ADAM10/17, and other metalloproteinases will degrade the tight junctions and adhesion protein connections between endothelial cells; the accumulation of nitric oxide (NO) and the increase of vascular endothelial growth factor (VEGF) and others further aggravate vascular dilation and constriction abnormalities, ultimately causing the disruption of intercellular connections between endothelial cells, widening the intercellular space, and resulting in vascular leakage.
