Thrombomodulin is essential for maintaining quiescence in vascular endothelial cells
Hemant Giri, Sumith R. Panicker, Xiaofeng Cai, Indranil Biswas, Hartmut Weiler, Alireza R. Rezaie
Abstract
Significance We demonstrate that deletion of thrombomodulin (TM) from endothelial cells confers inflammatory phenotype to TM-deficient ( TM −/− ) cells. This is based on the loss of integrity of VE-cadherin at cellular junctions, disrupted basal barrier permeability, and increased expression of cell adhesion molecules in TM −/− cells. Proinflammatory phenotype is rescued by reexpression of TM in TM −/− cells; however, soluble TM lacked this effect. Interestingly, instead of storage in Weibel–Palade bodies, VWF was secreted in TM −/− cells, thereby recruiting platelets to cell surfaces under flow conditions. Increased VWF and inflammatory foci were also observed in lungs of tamoxifen-treated ERcre-TM f/f mice. These results suggest cell-bound TM maintains a quiescent phenotype in vascular endothelial cells by regulating expression of procoagulant and proinflammatory molecules.