Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.
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 a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3897409?pdf=render |
| _version_ | 1818118075949514752 |
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| author | Henning Hagmann Verena Bossung Abdel Ali Belaidi Alexander Fridman S Ananth Karumanchi Ravi Thadhani Bernhard Schermer Peter Mallmann Guenter Schwarz Thomas Benzing Paul T Brinkkoetter |
| author_facet | Henning Hagmann Verena Bossung Abdel Ali Belaidi Alexander Fridman S Ananth Karumanchi Ravi Thadhani Bernhard Schermer Peter Mallmann Guenter Schwarz Thomas Benzing Paul T Brinkkoetter |
| author_sort | Henning Hagmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T04:48:33Z |
| format | Article |
| id | doaj.art-1115161493864d008de0287d7e1ed6e7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T04:48:33Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1115161493864d008de0287d7e1ed6e72022-12-22T01:20:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8525810.1371/journal.pone.0085258Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.Henning HagmannVerena BossungAbdel Ali BelaidiAlexander FridmanS Ananth KarumanchiRavi ThadhaniBernhard SchermerPeter MallmannGuenter SchwarzThomas BenzingPaul T BrinkkoetterRATIONALE: 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.http://europepmc.org/articles/PMC3897409?pdf=render |
| spellingShingle | Henning Hagmann Verena Bossung Abdel Ali Belaidi Alexander Fridman S Ananth Karumanchi Ravi Thadhani Bernhard Schermer Peter Mallmann Guenter Schwarz Thomas Benzing Paul T Brinkkoetter Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination. PLoS ONE |
| title | Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination. |
| title_full | Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination. |
| title_fullStr | Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination. |
| title_full_unstemmed | Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination. |
| title_short | Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination. |
| title_sort | low molecular weight heparin increases circulating sflt 1 levels and enhances urinary elimination |
| url | http://europepmc.org/articles/PMC3897409?pdf=render |
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