title: Differential effect of the low-molecular-weight heparin, dalteparin, and unfractionated heparin on microvascular endothelial cell hemostatic properties.
abstract: OBJECTIVE
  Heparins, including unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), are glycosaminoglycans that are largely used as anti-thrombotic drugs. While the mechanisms of their anticoagulant actions in blood have been extensively studied, their effects on the hemostatic properties of the endothelium are still under investigation. The aim of this study was to compare the antithrombotic effects of a LMWH, i.e. dalteparin, with UFH on both microvascular (human microvascular endothelial cells [HMEC-1]) and macrovascular (human umbilical vein endothelial cells [HUVEC]) endothelial cells.
  
  
  METHODS
  Endothelial cells were incubated with dalteparin or UFH and exposed to an inflammatory stimulus (i.e. lipopolysaccharide [LPS]). The following parameters were evaluated: tissue factor (TF procoagulant activity, antigen and mRNA), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM).
  
  
  RESULTS
  In HMEC-1 and HUVEC, both heparins inhibited LPS-induced endothelial cell TF expression. However, in HMEC-1, dalteparin was significantly more effective than UFH. Both heparins increased TFPI antigen release in HMEC-1 and HUVEC. Dalteparin also reversed LPS-induced reduction of TM in HMEC-1, while UFH did not.
  
  
  CONCLUSIONS
  These data show that both dalteparin and UFH suppress inflammatory-mediated TF expression and increase the anticoagulant properties of macro- and micro-vascular endothelial cells. However, dalteparin has significantly greater effects than UFH in the microvascular endothelium, a site that plays a central role in many processes involved in inflammation and thrombosis.
authors.affiliation: Department of Hematology-Oncology, Ospedali Riuniti di Bergamo, Largo Barozzi 1, 24128 Bergamo, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Vignoli
authors.forename: Marina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Donatella
authors.initials: D
authors.lastname: Balducci
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Anna
authors.initials: A
authors.lastname: Falanga
mesh_terms: D002478:Cells, Cultured; D017985:Dalteparin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D008833:Microcirculation / Q000187:drug effects*
chemical_list: D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D017985:Dalteparin