| 4 | Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C显示文摘Hepatitis C virus(HCV)infection is a major problem worldwide.HCV is not limited to liver disease but is frequently complicated by immune-mediated extrahepatic manifestations such as glomerulonephritis or vasculitis.A fatal complication of HCV-associated vascular disease is thrombosis.Polyriboinosinic:polyribocytidylic acid(poly(I:C)),a synthetic analog of viral RNA,induces a Toll-like receptor 3(TLR3)-dependent arteriolar thrombosis without significant thrombus formation in venules in vivo.These procoagulant effects are caused by increased endothelial synthesis of tissue factor and PAI-1 without platelet activation.In addition to human umbilical endothelial cells(HUVEC),human mesangial cells(HMC)produce procoagulatory factors,cytokines and adhesion molecules after stimulation with poly(I:C)or HCV-containing cryoprecipitates from a patient with a HCV infection as well.Activated protein C(APC)is able to prevent the induction of procoagulatory factors in HUVEC and HMC in vitro and blocks the effects of poly(I:C)and HCV-RNA on the expression of cytokines and adhesion molecules in HMC but not in HUVEC.In vivo,protein C inhibits poly(I:C)-induced arteriolar thrombosis.Thus,endothelial cells are de facto able to actively participate in immune-mediated vascular thrombosis caused by viral infections.Finally,we provide evidence for the ability of protein C to inhibit TLR3-mediated arteriolar thrombosis caused by HCV infection. | Philipp Blüm Joachim Pircher Monika Merkle Thomas Czermak Andrea Ribeiro Hanna Mannell Florian Krötz Alexander Hennrich Michael Spannagl Simone Köppel Erik Gaitzsch Markus Wörnle | 2017 | Cellular & Molecular Immunology2017，14，12： | 0 |
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