Recombinant Soluble Thrombomodulin Reduces Lipopolysaccharide-Induced Endothelial Cellular Stiffening

Recent studies have indicated that endothelial cell increases cellular stiffness upon inflammation and that stiff endothelium of atherosclerotic region and aged vessels is favor to monocyte adhesion and accumulation. The anticoagulant recombinant soluble thrombomodulin (rsTM) suppresses inflammatory response of endothelial cells (ECs), however effect of rsTM on endothelial cellular stiffness remain elusive. In this study, we investigated the impact of rsTM on lipopolysaccharide (LPS)-induced endothelial cellular stiffening. We employed atomic force microscopy to measure the stiffness of cultured human umbilical vein ECs after LPS stimulation and/or rsTM treatment. ECs increased their stiffness after 4 hours of stimulation, and rsTM reduced LPS-induced cellular stiffening through the attenuation of actin fiber and focal adhesion formation and via the improvement of gap junction functionality. LPS-induced ECs stiffening facilitated THP-1 cell adhesion, whereas rsTM suppressed THP-1 cell adhesion by reducing cellular stiffness. Our finding that rsTM regulates monocyte adhesion via reducing endothelial cellular stiffness suggests that rsTM treatment holds some promise for the treatment of vascular inflammatory diseases, such as sepsis. Oral Sessions