PMID- 22504459
OWN - NLM
STAT- MEDLINE
DCOM- 20120920
LR  - 20120604
IS  - 1569-1802 (Electronic)
IS  - 0945-053X (Linking)
VI  - 31
IP  - 5
DP  - 2012 Jun
TI  - Glycosaminoglycan backbone is not required for the modulation of hemostasis: 
      effect of different heparin derivatives and non-glycosaminoglycan analogs.
PG  - 308-16
LID - 10.1016/j.matbio.2012.03.001 [doi]
AB  - Heparin and its derivatives are known to regulate a variety of pathophysiological 
      events related to vascular biology. In the present manuscript we examine a 
      variety of heparinomimetics biochemically (electrophoretic behavior and enzymatic 
      degradation) and pharmacologically (in vitro anticoagulant activity and in vivo 
      hemorrhagic and antithrombotic tests) as well as their interactions with cells 
      from the vessel wall using a time resolved fluorometric method and confocal 
      microscopy. Data were determined for unfractionated heparin (UFH), enoxaparin, 
      synthetic heparin pentasaccharide, C3 heparin derived oligosaccharides and 
      phosphosulfomannan (PI-88). While being structurally distinct from UFH, all 
      compounds exhibited anticoagulant, antithrombotic and hemorrhagic activities. In 
      addition, besides the pentasaccharide, they all stimulated the synthesis of an 
      antithrombotic heparan sulfate present at the cell surface and secreted by 
      endothelial cells. Also, like UFH, they interacted with both endothelial and 
      smooth muscle cells and dislodged UFH from its binding sites in a dose dependent 
      manner but, with distinct saturable curves showing that the binding of polymeric 
      structures to extracellular matrix (ECM) proteins does not depend on a 
      glycosaminoglycan backbone. The data also suggest a common pathway, which does 
      not depend on the presence of the conventionally accepted antithrombin binding 
      pentasaccharide, for ECM dependent activity of the heparinomimetic stimulated 
      synthesis of antithrombotic heparan sulfate. Notably, although of similar 
      molecular weight as well as polymeric backbone, the synthetic heparin 
      pentasaccharide showed significant hemorrhagic action and negligible 
      antithrombotic activity in a venous thrombosis model, contrasting with C3, that 
      displayed negligible hemorrhagic effect and potent antithrombotic action. These 
      results provide evidence that structurally unrelated polymers can elicit similar 
      hemostatic activities and show that polymeric sequence is not always crucial for 
      certain activities. The results also suggest that non-GAG structures may provide 
      an alternative route for the pharmaceutical control of hemostasis.
CI  - Copyright (c) 2012 International Society of Matrix Biology. Published by Elsevier 
      B.V. All rights reserved.
FAU - Boucas, Rodrigo I
AU  - Boucas RI
AD  - Disciplina de Biologia Molecular, Departamento de Bioquimica, Universidade 
      Federal de Sao Paulo, SP, Brazil.
FAU - Jarrouge-Boucas, Thais R
AU  - Jarrouge-Boucas TR
FAU - Lima, Marcelo A
AU  - Lima MA
FAU - Trindade, Edvaldo S
AU  - Trindade ES
FAU - Moraes, Fabio A
AU  - Moraes FA
FAU - Cavalheiro, Renan P
AU  - Cavalheiro RP
FAU - Tersariol, Ivarne L S
AU  - Tersariol IL
FAU - Hoppenstead, Debra
AU  - Hoppenstead D
FAU - Fareed, Jawed
AU  - Fareed J
FAU - Nader, Helena B
AU  - Nader HB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120406
PL  - Netherlands
TA  - Matrix Biol
JT  - Matrix biology : journal of the International Society for Matrix Biology
JID - 9432592
RN  - 0 (Anticoagulants)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Oligosaccharides)
RN  - 0 (phosphomannopentaose sulfate)
RN  - 9005-49-6 (Heparin)
RN  - EC 4.2.2.7 (Heparin Lyase)
SB  - IM
MH  - Animals
MH  - Anticoagulants/pharmacology
MH  - Binding Sites
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/chemistry/drug effects
MH  - Extracellular Matrix/chemistry/*drug effects
MH  - Fibrinolytic Agents/pharmacology
MH  - *Hemostasis
MH  - Heparin/*analogs & derivatives/*pharmacology
MH  - Heparin Lyase/chemistry
MH  - Molecular Weight
MH  - Myocytes, Smooth Muscle/chemistry/drug effects
MH  - Oligosaccharides/pharmacology
MH  - Protein Binding
MH  - Proteolysis
MH  - Rabbits
MH  - Rats
MH  - Substrate Specificity
EDAT- 2012/04/17 06:00
MHDA- 2012/09/21 06:00
CRDT- 2012/04/17 06:00
PHST- 2012/01/20 00:00 [received]
PHST- 2012/03/10 00:00 [revised]
PHST- 2012/03/23 00:00 [accepted]
PHST- 2012/04/17 06:00 [entrez]
PHST- 2012/04/17 06:00 [pubmed]
PHST- 2012/09/21 06:00 [medline]
AID - S0945-053X(12)00050-9 [pii]
AID - 10.1016/j.matbio.2012.03.001 [doi]
PST - ppublish
SO  - Matrix Biol. 2012 Jun;31(5):308-16. doi: 10.1016/j.matbio.2012.03.001. Epub 2012 
      Apr 6.