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.
Methods and 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angioplasty, Balloon, Coronary
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Animals
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Cells, Cultured
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Coronary Angiography
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Coronary Artery Disease / blood
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Coronary Artery Disease / diagnostic imaging
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Coronary Artery Disease / therapy
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Extracellular Matrix / drug effects*
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Extracellular Matrix / metabolism
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Fibrinolytic Agents / administration & dosage
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Fibrinolytic Agents / pharmacology*
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Heparin / administration & dosage
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Heparin / pharmacology*
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Heparin Lyase / pharmacology
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Humans
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In Vitro Techniques
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Injections, Intravenous
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Male
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Mice
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Mice, Inbred C57BL
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Models, Animal
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Polysaccharide-Lyases / pharmacology
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Vascular Endothelial Growth Factor Receptor-1 / blood*
Substances
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Fibrinolytic Agents
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Heparin
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Flt1 protein, mouse
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Vascular Endothelial Growth Factor Receptor-1
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Polysaccharide-Lyases
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Heparin Lyase
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heparitinsulfate lyase