PMID- 32762584
OWN - NLM
STAT- MEDLINE
DCOM- 20211228
LR  - 20211228
IS  - 1369-1635 (Electronic)
IS  - 0953-7104 (Linking)
VI  - 32
IP  - 6
DP  - 2021 Aug 18
TI  - Factor Xa and thrombin induce endothelial progenitor cell activation. The effect 
      of direct oral anticoagulants.
PG  - 807-814
LID - 10.1080/09537104.2020.1802413 [doi]
AB  - Factor Xa (FXa) and thrombin exert non-hemostatic cellular actions primarily 
      mediated through protease-activated receptors (PARs). We investigated the effect 
      of FXa and thrombin on human late-outgrowth endothelial cells (OECs), a type of 
      endothelial progenitor cells (EPCs), and on human umbilical vein endothelial 
      cells (HUVECs). The effect of direct oral anticoagulants (DOACs), rivaroxaban and 
      dabigatran, was also studied. The membrane expression of intercellular adhesion 
      molecule-1 (ICAM-1) and the secretion of monocyte chemoattractant protein-1 
      (MCP-1) were used as cell activation markers. FXa and thrombin increase the 
      ICAM-1 expression and the MCP-1 secretion on both cells, being higher on OECs. 
      Vorapaxar, a specific PAR-1 antagonist, completely inhibits FXa-induced 
      activation of both cells and thrombin-induced HUVEC activation, but only 
      partially thrombin-induced OEC activation. Furthermore, thrombin-receptor 
      activating peptide; TRAP-6, only partially activates OECs. OECs do not 
      membrane-express PAR-4, therefore it may not be involved on thrombin-induced OEC 
      activation. Rivaroxaban and dabigatran inhibit OEC and HUVEC activation by FXa 
      and thrombin, respectively. Rivaroxaban enhances thrombin-induced OEC and HUVEC 
      activation, which is completely inhibited by vorapaxar. The inhibition of OEC and 
      HUVEC activation by vorapaxar and DOACs may represent a new pleiotropic effect of 
      these drugs. The pathophysiological and clinical significance of our findings 
      need to be established.
FAU - Papadaki, Styliani
AU  - Papadaki S
AD  - Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of 
      Chemistry, University of Ioannina, Ioannina, Greece.
FAU - Sidiropoulou, Sofia
AU  - Sidiropoulou S
AD  - Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of 
      Chemistry, University of Ioannina, Ioannina, Greece.
FAU - Moschonas, Iraklis C
AU  - Moschonas IC
AD  - Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of 
      Chemistry, University of Ioannina, Ioannina, Greece.
FAU - Tselepis, Alexandros D
AU  - Tselepis AD
AD  - Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of 
      Chemistry, University of Ioannina, Ioannina, Greece.
LA  - eng
PT  - Journal Article
DEP - 20200807
PL  - England
TA  - Platelets
JT  - Platelets
JID - 9208117
RN  - 0 (Anticoagulants)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - Administration, Oral
MH  - Anticoagulants/pharmacology/*therapeutic use
MH  - Endothelial Progenitor Cells/*metabolism
MH  - Factor Xa/*metabolism
MH  - Humans
MH  - Thrombin/*metabolism
OTO - NOTNLM
OT  - Dabigatran
OT  - Factor Xa
OT  - endothelial progenitor cells
OT  - rivaroxaban
OT  - thrombin
OT  - vorapaxar
EDAT- 2020/08/09 06:00
MHDA- 2021/12/29 06:00
CRDT- 2020/08/09 06:00
PHST- 2020/08/09 06:00 [pubmed]
PHST- 2021/12/29 06:00 [medline]
PHST- 2020/08/09 06:00 [entrez]
AID - 10.1080/09537104.2020.1802413 [doi]
PST - ppublish
SO  - Platelets. 2021 Aug 18;32(6):807-814. doi: 10.1080/09537104.2020.1802413. Epub 
      2020 Aug 7.