PMID- 32559568
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 193
DP  - 2020 Sep
TI  - Unfractionated heparin inhibits histone-mediated coagulation activation and 
      thrombosis in mice.
PG  - 122-129
LID - S0049-3848(20)30241-3 [pii]
LID - 10.1016/j.thromres.2020.06.007 [doi]
AB  - INTRODUCTION: Histones play pivotal roles in the pathophysiology of sepsis. 
      Different studies have reported that unfractionated heparin (UFH) can improve 
      histone-mediated organ dysfunction. However, in such studies, UFH was usually 
      pretreated or injected with histones concurrently, which was obviously 
      inconsistent with clinical practice. Therefore, this study aimed to figure out 
      whether UFH can inhibit histone-induced coagulation activation and thrombosis 
      when histones have caused coagulation disorder already. METHODS: Male C57/BL6 
      mice of average weight ~22 g were randomly divided into three groups. The histone 
      group was injected with histones 50 mg/kg through the tail vein. The 
      histone + UFH group was injected with UFH (400 U/kg) through the tail vein 1 h or 
      6 h after the induction of histones. The control group was injected with equal 
      volume of sterile saline. The lungs were harvested 3 h after UFH administration. 
      In survival studies, mice were treated with UFH (800 U/kg, n = 10) or sterile 
      saline (n = 10) intravenously after histones (75 mg/kg) injection and observed 
      for 7 days. RESULTS: 1) UFH improved survival rate in mice injected with lethal 
      doses of histones; 2) UFH alleviated histone-induced lung injury and pulmonary 
      edema; 3) UFH improved histone-induced endothelial cell injury; 4) UFH improved 
      histone-mediated high expression of TF, PAI-1, fibrinogen and low expression of 
      TM. CONCLUSION: UFH can effectively attenuate histone-induced lung injury, 
      coagulation activation and thrombosis.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Li, Lu
AU  - Li L
AD  - Department of Critical Care Medicine, The First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, 
      China.
FAU - Yu, Sihan
AU  - Yu S
AD  - Department of Critical Care Medicine, The First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, 
      China.
FAU - Fu, Sifeng
AU  - Fu S
AD  - Department of Critical Care Medicine, The First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, 
      China.
FAU - Ma, Xiaochun
AU  - Ma X
AD  - Department of Critical Care Medicine, The First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, 
      China.
FAU - Li, Xu
AU  - Li X
AD  - Department of Critical Care Medicine, The First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, 
      China. Electronic address: vincentzh002@outlook.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200605
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Anticoagulants)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Histones)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/pharmacology/therapeutic use
MH  - Blood Coagulation
MH  - Fibrinolytic Agents/pharmacology
MH  - *Heparin/pharmacology/therapeutic use
MH  - Histones
MH  - Male
MH  - Mice
MH  - *Thrombosis/drug therapy
OTO - NOTNLM
OT  - Coagulation activation
OT  - Histone
OT  - Lung injury
OT  - Unfractionated heparin
COIS- Declaration of competing interest There were no conflicts of interest.
EDAT- 2020/06/20 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/06/20 06:00
PHST- 2020/02/21 00:00 [received]
PHST- 2020/05/26 00:00 [revised]
PHST- 2020/06/02 00:00 [accepted]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
AID - S0049-3848(20)30241-3 [pii]
AID - 10.1016/j.thromres.2020.06.007 [doi]
PST - ppublish
SO  - Thromb Res. 2020 Sep;193:122-129. doi: 10.1016/j.thromres.2020.06.007. Epub 2020 
      Jun 5.