title: Heparin strongly induces soluble fms-like tyrosine kinase 1 release in vivo and in vitro--brief report.
abstract: OBJECTIVE
  Soluble fms-like tyrosine kinase 1 (sFlt1) is involved in the pathophysiology of preeclampsia and coronary artery disease. Because sFlt1 has a heparin-binding site, we investigated whether or not heparin releases sFlt1 from the extracellular matrix.
  
  
  RESULTS
  We measured sFlt1 before and after heparin administration in 135 patients undergoing coronary angiography, percutanous coronary intervention, or both. sFlt1 was increased directly after heparin administration (from 254 to 13,440 pg/mL) and returned to baseline within 10 hours. Umbilical veins and endothelial cells treated with heparin released sFlt1. Heparinase I and III also increased sFlt1. Mice treated with heparin had elevated sFlt1 serum levels. Their serum inhibited endothelial tube formation.
  
  
  CONCLUSIONS
  Heparin releases sFlt1 by displacing the sFlt1 heparin-binding site from heparan sulfate proteoglycans. Heparin could induce an antiangiogenic state.
authors: Department of Cardiology, Campus Virchow Klinikum, Charité–Universitätsmedizin Berlin, Germany.
authors: Julia
authors: J
authors: Searle
authors: Martin
authors: M
authors: Mockel
authors: Stefanie
authors: S
authors: Gwosc
authors: Saul A
authors: SA
authors: Datwyler
authors: Fatimunnisa
authors: F
authors: Qadri
authors: Gesa I
authors: GI
authors: Albert
authors: Fabian
authors: F
authors: Holert
authors: Annette
authors: A
authors: Isbruch
authors: Lars
authors: L
authors: Klug
authors: Dominik N
authors: DN
authors: Muller
authors: Ralf
authors: R
authors: Dechend
authors: Reinhold
authors: R
authors: Muller
authors: Joern O
authors: JO
authors: Vollert
authors: Anna
authors: A
authors: Slagman
authors: Christian
authors: C
authors: Mueller
authors: Florian
authors: F
authors: Herse
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D002478:Cells, Cultured; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D005343:Fibrinolytic Agents; D006493:Heparin; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase; C021349:heparitinsulfate lyase