PMID- 16461305 OWN - NLM STAT- MEDLINE DCOM- 20060706 LR - 20220309 IS - 1592-8721 (Electronic) IS - 0390-6078 (Linking) VI - 91 IP - 2 DP - 2006 Feb TI - Differential effect of the low-molecular-weight heparin, dalteparin, and unfractionated heparin on microvascular endothelial cell hemostatic properties. PG - 207-14 AB - BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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. INTERPRETATION AND 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. FAU - Vignoli, Alfonso AU - Vignoli A AD - Department of Hematology-Oncology, Ospedali Riuniti di Bergamo, Largo Barozzi 1, 24128 Bergamo, Italy. FAU - Marchetti, Marina AU - Marchetti M FAU - Balducci, Donatella AU - Balducci D FAU - Barbui, Tiziano AU - Barbui T FAU - Falanga, Anna AU - Falanga A LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Italy TA - Haematologica JT - Haematologica JID - 0417435 RN - 0 (Heparin, Low-Molecular-Weight) RN - 9005-49-6 (Heparin) RN - S79O08V79F (Dalteparin) SB - IM EIN - Haematologica. 2006 May;91(5):620 CIN - Haematologica. 2006 Feb;91(2):149a. PMID: 16461295 MH - Cells, Cultured MH - Dalteparin/pharmacology MH - Endothelium, Vascular/cytology/*drug effects MH - Hemostasis/*drug effects MH - Heparin/*pharmacology MH - Heparin, Low-Molecular-Weight/pharmacology MH - Humans MH - Microcirculation/*drug effects EDAT- 2006/02/08 09:00 MHDA- 2006/07/11 09:00 CRDT- 2006/02/08 09:00 PHST- 2006/02/08 09:00 [pubmed] PHST- 2006/07/11 09:00 [medline] PHST- 2006/02/08 09:00 [entrez] PST - ppublish SO - Haematologica. 2006 Feb;91(2):207-14.