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- Title
Unfractionated heparin protects the protein C system against lipopolysaccharide-induced damage in vivo and in vitro.
- Authors
DONGMEI ZHAO; RENYU DING; YINA LIU; XIAOHAN YIN; ZHIDAN ZHANG; XIAOCHUN MA
- Abstract
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 κB 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.
- Subjects
PROTEIN C; LIPOPOLYSACCHARIDES; SEPSIS; THROMBOMODULIN; ENDOTHELIAL cells; GENETICS; THERAPEUTICS
- Publication
Experimental & Therapeutic Medicine, 2017, Vol 14, Issue 6, p5515
- ISSN
1792-0981
- Publication type
Article
- DOI
10.3892/etm.2017.5236