Figure 1.

Sepsis, endothelial dysfunction, and microcirculation. In sepsis, endothelial cells (ECs) play crucial roles in mediating microcirculatory disorders by influencing inflammation, vascular permeability, coagulation, and vasomotor function. Lipopolysaccharides (LPS), bacteria, and viruses bind to receptors on the surface of ECs, triggering an inflammatory cascade through various signaling pathways. This cascade promotes the adhesion and accumulation of white blood cells in ECs, exacerbating microcirculation disorders and further promoting disease progression. The inflammatory response to vascular permeability increases the expression of adhesion molecules, increasing permeability and further aggravating the inflammatory response. During coagulation, inflammatory mediators stimulate an increase in procoagulant factors and a decrease in anticoagulant factors, leading to microthrombus formation. ECs exhibit anticoagulant effects via the expression of substances such as tissue factor pathway inhibitors, thrombomodulin, and the EC protein C receptor. In vasomotor disorders, a decrease in eNOS and an increase in iNOS expression in ECs, along with the activation of the PLC pathway due to elevated ET-1, contribute to vasomotor dysfunction. LPS: lipopolysaccharide; NF-κB: nuclear factor-Κb; MAPK: mitogen-activated protein kinase; JAK: Janus kinase; STAT: signal transducer and activator of transcription; ZO-1: zonula occludens-1; PI3K: phosphatidylinositol-3-kinase; AKT: protein kinase B; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; TFPI: tissue factor pathway inhibitor; NO: nitric oxide; PKC: protein kinase C; eNOS: endothelial NO synthase; iNOS: inducible nitric oxide synthase; PLC: phospholipase C; ET-1: endothelin-1; ICAM-1: intercellular adhesion molecule-1; VCAM-1: vascular cell adhesion molecule-1; TF: transcription factor; WBC: white blood cell.

Table 1.

Biomarkers of sepsis-induced endothelial injury

Table 2.

Therapeutic strategies targeting endothelial injury in sepsis