Characterization of coagulation factor synthesis in nine human primary cell types

Abstract

The coagulation/fibrinolysis system is essential for wound healing after vascular injury. According to the standard paradigm, the synthesis of most coagulation factors is restricted to liver, platelets and endothelium. We challenged this interpretation by measuring coagulation factors in nine human primary cell types. FX mRNA was expressed by fibroblasts, visceral preadipocytes/adipocytes and hepatocytes, but not in macrophages or other cells. All cells expressed FVIII except endothelial cells. Fibroblasts, endothelial cells and macrophages produced thrombomodulin but not FV. Interestingly, vascular-related cells (platelets/monocytes) that expressed FV did not express FX and vice versa. Monocytes expressed FV, FVIII and FXIIIA, which are positive regulators of clot formation, but these cells also contained thrombomodulin, a negative regulator of coagulation. Our data show that the expression of coagulation factors is much more complex than previously thought, and we speculate that this intricate regulation of coagulation factor expression is necessary for correct fine-tuning of fibrinogenesis versus fibrinolysis.