PMID- 29285085
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 14
IP  - 6
DP  - 2017 Dec
TI  - Unfractionated heparin protects the protein C system against 
      lipopolysaccharide-induced damage in vivo and in vitro.
PG  - 5515-5522
LID - 10.3892/etm.2017.5236 [doi]
AB  - Activation of protein C is greatly enhanced by the presence of thrombomodulin 
      (TM) and endothelial protein C receptor (EPCR) on the endothelial surface. 
      Impairment of the anticoagulant protein C system occurs during endotoxemia and 
      contributes to sepsis-associated hypercoagulability. Previous studies have 
      demonstrated that unfractionated heparin (UFH) can attenuate coagulation in 
      endotoxemic mice. However, whether UFH has an effect on the protein C system 
      remains to be elucidated. The current study evaluated the therapeutic effect of 
      UFH on the protein C system in a mouse model of lipopolysaccharide (LPS)-induced 
      sepsis, and further investigated the effect of UFH on the expression of TM and 
      EPCR in vitro using human umbilical vein endothelial cells (HUVECs). The in vivo 
      data indicated that UFH preconditioning attenuated the decline in circulating 
      activated protein C following LPS administration, and also reduced LPS-induced 
      shedding of TM and EPCR. In HUVECs, LPS stimulation led to the downregulation of 
      TM and EPCR expression, and UFH dose-dependently restored the mRNA and protein 
      levels of TM and EPCR. In addition, UFH inhibited the LPS-induced activation of 
      mitogen-activated protein kinase 14, proto-oncogene tyrosine-protein kinase Src 
      and nuclear factor kappaB signaling in HUVECs. In summary, these results suggest that 
      UFH has a protective effect on the protein C system during sepsis. Thus, UFH may 
      be a candidate therapeutic agent for the treatment of patients with sepsis.
FAU - Zhao, Dongmei
AU  - Zhao D
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
FAU - Ding, Renyu
AU  - Ding R
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
FAU - Liu, Yina
AU  - Liu Y
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
FAU - Yin, Xiaohan
AU  - Yin X
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
FAU - Zhang, Zhidan
AU  - Zhang Z
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
FAU - Ma, Xiaochun
AU  - Ma X
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170929
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC5740512
OTO - NOTNLM
OT  - endothelial protein C receptor
OT  - lipopolysaccharide
OT  - protein C
OT  - sepsis
OT  - thrombomodulin
OT  - unfractionated heparin
EDAT- 2017/12/30 06:00
MHDA- 2017/12/30 06:01
PMCR- 2017/09/29
CRDT- 2017/12/30 06:00
PHST- 2017/01/03 00:00 [received]
PHST- 2017/07/14 00:00 [accepted]
PHST- 2017/12/30 06:00 [entrez]
PHST- 2017/12/30 06:00 [pubmed]
PHST- 2017/12/30 06:01 [medline]
PHST- 2017/09/29 00:00 [pmc-release]
AID - ETM-0-0-5236 [pii]
AID - 10.3892/etm.2017.5236 [doi]
PST - ppublish
SO  - Exp Ther Med. 2017 Dec;14(6):5515-5522. doi: 10.3892/etm.2017.5236. Epub 2017 Sep 
      29.