PMID- 38068988
OWN - NLM
STAT- MEDLINE
DCOM- 20231220
LR  - 20231220
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 23
DP  - 2023 Nov 23
TI  - Zn(2+) Differentially Influences the Neutralisation of Heparins by HRG, 
      Fibrinogen, and Fibronectin.
LID - 10.3390/ijms242316667 [doi]
LID - 16667
AB  - For coagulation to be initiated, anticoagulant glycosaminoglycans (GAGs) such as 
      heparins need to be neutralised to allow fibrin clot formation. Platelet 
      activation triggers the release of several proteins that bind GAGs, including 
      histidine-rich glycoprotein (HRG), fibrinogen, and fibronectin. Zn(2+) ions are 
      also released and have been shown to enhance the binding of HRG to heparins of a 
      high molecular weight (HMWH) but not to those of low molecular weight (LMWH). The 
      effect of Zn(2+) on fibrinogen and fibronectin binding to GAGs is unknown. Here, 
      chromogenic assays were used to measure the anti-factor Xa and anti-thrombin 
      activities of heparins of different molecular weights and to assess the effects 
      of HRG, fibrinogen, fibronectin, and Zn(2+). Surface plasmon resonance was also 
      used to examine the influence of Zn(2+) on the binding of fibrinogen to heparins 
      of different molecular weights. Zn(2+) had no effect on the neutralisation of 
      anti-factor Xa (FXa) or anti-thrombin activities of heparin by fibronectin, 
      whereas it enhanced the neutralisation of unfractionated heparin (UFH) and HMWH 
      by both fibrinogen and HRG. Zn(2+) also increased neutralisation of the anti-FXa 
      activity of LMWH by fibrinogen but not HRG. SPR showed that Zn(2+) increased 
      fibrinogen binding to both UFH and LMWH in a concentration-dependent manner. The 
      presented results reveal that an increase in Zn(2+) concentration has 
      differential effects upon anticoagulant GAG neutralisation by HRG and fibrinogen, 
      with implications for modulating anti-coagulant activity in plasma.
FAU - Sobczak, Amelie I S
AU  - Sobczak AIS
AUID- ORCID: 0000-0003-4892-7203
AD  - School of Medicine, University of St Andrews, St. Andrews KY16 9TF, UK.
FAU - Ajjan, Ramzi A
AU  - Ajjan RA
AUID- ORCID: 0000-0002-1636-3725
AD  - Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 
      Leeds LS2 3AA, UK.
FAU - Stewart, Alan J
AU  - Stewart AJ
AUID- ORCID: 0000-0003-4580-1840
AD  - School of Medicine, University of St Andrews, St. Andrews KY16 9TF, UK.
LA  - eng
GR  - PG/15/9/31270/BHF_/British Heart Foundation/United Kingdom
GR  - FS/15/42/3155/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
DEP - 20231123
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anticoagulants)
RN  - 9001-32-5 (Fibrinogen)
RN  - 0 (Fibronectins)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Hemostatics)
RN  - 9005-49-6 (Heparin)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (histidine-rich proteins)
RN  - EC 3.4.21.5 (Thrombin)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Anticoagulants
MH  - Fibrinogen/metabolism
MH  - Fibronectins
MH  - Glycosaminoglycans
MH  - *Hemostatics
MH  - *Heparin/pharmacology/metabolism
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Thrombin/chemistry
MH  - Zinc/metabolism
PMC - PMC10706850
OTO - NOTNLM
OT  - coagulation factors
OT  - factor Xa
OT  - fibrinogen/fibrin
OT  - thrombin
OT  - zinc
COIS- The authors declare no conflict of interest.
EDAT- 2023/12/09 10:43
MHDA- 2023/12/17 09:45
PMCR- 2023/11/23
CRDT- 2023/12/09 01:13
PHST- 2023/11/08 00:00 [received]
PHST- 2023/11/19 00:00 [revised]
PHST- 2023/11/22 00:00 [accepted]
PHST- 2023/12/17 09:45 [medline]
PHST- 2023/12/09 10:43 [pubmed]
PHST- 2023/12/09 01:13 [entrez]
PHST- 2023/11/23 00:00 [pmc-release]
AID - ijms242316667 [pii]
AID - ijms-24-16667 [pii]
AID - 10.3390/ijms242316667 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Nov 23;24(23):16667. doi: 10.3390/ijms242316667.