Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy

Figure 3 Proposed model linking radiation-induced endothelial dysfunction to chronic inflammation and progressive intestinal fibrosis via chronic PAR₁ activation. Radiation causes TM deficiency in endothelial cells, leading to insufficient “scavenging” of locally formed thrombin. Thrombin exerts pro-coagulant, pro-inflammatory, mitogenic, and pro-fibrogenic effects on mesenchymal cells (smooth muscle cells, fibroblasts, and myofibroblasts), as well as other cell types in the irradiated tissue. Feed-back by cytokines and other inflammatory mediators sustains the endothelial TM deficiency and thus contributes to the chronicity of radiation injury.