PMID- 26325534 OWN - NLM STAT- MEDLINE DCOM- 20161013 LR - 20230717 IS - 1600-0641 (Electronic) IS - 0168-8278 (Print) IS - 0168-8278 (Linking) VI - 64 IP - 1 DP - 2016 Jan TI - Hepatocyte tissue factor contributes to the hypercoagulable state in a mouse model of chronic liver injury. PG - 53-9 LID - S0168-8278(15)00588-7 [pii] LID - 10.1016/j.jhep.2015.08.017 [doi] AB - BACKGROUND & AIMS: Patients with chronic liver disease and cirrhosis have a dysregulated coagulation system and are prone to thrombosis. The basis for this hypercoagulable state is not completely understood. Tissue factor (TF) is the primary initiator of coagulation in vivo. Patients with cirrhosis have increased TF activity in white blood cells and circulating microparticles. The aim of our study was to determine the contribution of TF to the hypercoagulable state in a mouse model of chronic liver injury. METHODS: We measured levels of TF activity in the liver, white blood cells and circulating microparticles, and a marker of activation of coagulation (thrombin-antithrombin complexes (TATc)) in the plasma of mice subjected to bile duct ligation for 12days. We used wild-type mice, mice with a global TF deficiency (low TF mice), and mice deficient for TF in either myeloid cells (TF(flox/flox),LysMCre mice) or in hepatocytes (TF(flox/flox),AlbCre). RESULTS: Wild-type mice with liver injury had increased levels of white blood cell, microparticle TF activity and TATc compared to sham mice. Low TF mice and mice lacking TF in hepatocytes had reduced levels of TF in the liver and in microparticles and exhibited reduced activation of coagulation without a change in liver fibrosis. In contrast, mice lacking TF in myeloid cells had reduced white blood cell TF but no change in microparticle TF activity or TATc. CONCLUSIONS: Hepatocyte TF activates coagulation in a mouse model of chronic liver injury. TF may contribute to the hypercoagulable state associated with chronic liver diseases in patients. CI - Copyright (c) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. FAU - Rautou, Pierre-Emmanuel AU - Rautou PE AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Service d'Hepatologie, Hopital Beaujon, Assistance Publique-Hopitaux de Paris, Clichy, France. Electronic address: pierre-emmanuel.rautou@inserm.fr. FAU - Tatsumi, Kohei AU - Tatsumi K AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Antoniak, Silvio AU - Antoniak S AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Owens, A Phillip 3rd AU - Owens AP 3rd AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Sparkenbaugh, Erica AU - Sparkenbaugh E AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Holle, Lori A AU - Holle LA AD - Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Wolberg, Alisa S AU - Wolberg AS AD - Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Kopec, Anna K AU - Kopec AK AD - Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, USA. FAU - Pawlinski, Rafal AU - Pawlinski R AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Luyendyk, James P AU - Luyendyk JP AD - Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, USA. FAU - Mackman, Nigel AU - Mackman N AD - Department of Medicine, Division of Hematology and Oncology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. LA - eng GR - R56 HL094740/HL/NHLBI NIH HHS/United States GR - 1F32-HL099175-03/HL/NHLBI NIH HHS/United States GR - R00 HL116786/HL/NHLBI NIH HHS/United States GR - R01 ES017537/ES/NIEHS NIH HHS/United States GR - R01 HL096679/HL/NHLBI NIH HHS/United States GR - P50HL120100/HL/NHLBI NIH HHS/United States GR - F32 HL099175/HL/NHLBI NIH HHS/United States GR - ES017537/ES/NIEHS NIH HHS/United States GR - T32-HL007149-37/HL/NHLBI NIH HHS/United States GR - T32 HL007149/HL/NHLBI NIH HHS/United States GR - R01 HL126974/HL/NHLBI NIH HHS/United States GR - R01 HL095096/HL/NHLBI NIH HHS/United States GR - HL095096/HL/NHLBI NIH HHS/United States GR - P50 HL120100/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150829 PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 9035-58-9 (Thromboplastin) SB - IM MH - Animals MH - Cells, Cultured MH - Chronic Disease MH - Disease Models, Animal MH - Hepatocytes/*physiology MH - Humans MH - Liver Diseases/*blood MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Thrombophilia/*etiology MH - Thromboplastin/*physiology PMC - PMC4691429 MID - NIHMS719805 OTO - NOTNLM OT - Coagulation OT - Liver injury OT - Microparticle OT - Thrombosis COIS- Conflict of Interest Authors have no direct and indirect conflicts of interest. EDAT- 2015/09/02 06:00 MHDA- 2016/10/14 06:00 PMCR- 2017/01/01 CRDT- 2015/09/02 06:00 PHST- 2015/03/30 00:00 [received] PHST- 2015/08/13 00:00 [revised] PHST- 2015/08/19 00:00 [accepted] PHST- 2015/09/02 06:00 [entrez] PHST- 2015/09/02 06:00 [pubmed] PHST- 2016/10/14 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - S0168-8278(15)00588-7 [pii] AID - 10.1016/j.jhep.2015.08.017 [doi] PST - ppublish SO - J Hepatol. 2016 Jan;64(1):53-9. doi: 10.1016/j.jhep.2015.08.017. Epub 2015 Aug 29.