Universität zu Köln

Hagmann, Henning, Bossung, Verena ORCID: 0000-0001-5561-1827, Belaidi, Abdel Ali, Fridman, Alexander, Karumanchi, S. Ananth, Thadhani, Ravi, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Mallmann, Peter, Schwarz, Guenter ORCID: 0000-0002-2118-9338, Benzing, Thomas and Brinkkoetter, Paul T. (2014). Low-Molecular Weight Heparin Increases Circulating sFlt-1 Levels and Enhances Urinary Elimination. PLoS One, 9 (1). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Rationale: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1), an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. Objective: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. Methods and Results: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. Conclusion: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Bossung, Verena UNSPECIFIED orcid.org/0000-0001-5561-1827 UNSPECIFIED Belaidi, Abdel Ali UNSPECIFIED UNSPECIFIED UNSPECIFIED Fridman, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Karumanchi, S. Ananth UNSPECIFIED UNSPECIFIED UNSPECIFIED Thadhani, Ravi UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Mallmann, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Paul T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-448331
DOI:	10.1371/journal.pone.0085258
Journal or Publication Title:	PLoS One
Volume:	9
Number:	1
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLACENTAL GROWTH-FACTOR; TYROSINE KINASE 1; ANGIOGENIC FACTORS; SOLUBLE ENDOGLIN; EARLY-PREGNANCY; WOMEN; RISK; PREECLAMPSIA; PERMSELECTIVITY; MACROMOLECULES Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/44833