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
  • View Affiliations

  • Published online on: September 29, 2017     https://doi.org/10.3892/etm.2017.5236
  • Pages:5515-5522
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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.

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
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APA
Zhao, D., Ding, R., Liu, Y., Yin, X., Zhang, Z., & Ma, X. (2017). Unfractionated heparin protects the protein C system against lipopolysaccharide‑induced damage in vivo and in vitro. Experimental and Therapeutic Medicine, 14, 5515-5522. https://doi.org/10.3892/etm.2017.5236
MLA
Zhao, D., Ding, R., Liu, Y., Yin, X., Zhang, Z., Ma, X."Unfractionated heparin protects the protein C system against lipopolysaccharide‑induced damage in vivo and in vitro". Experimental and Therapeutic Medicine 14.6 (2017): 5515-5522.
Chicago
Zhao, D., Ding, R., Liu, Y., Yin, X., Zhang, Z., Ma, X."Unfractionated heparin protects the protein C system against lipopolysaccharide‑induced damage in vivo and in vitro". Experimental and Therapeutic Medicine 14, no. 6 (2017): 5515-5522. https://doi.org/10.3892/etm.2017.5236