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.
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 sFlt1heparin-binding site from heparan sulfate proteoglycans. Heparin could induce an antiangiogenic state.
Authors: Jean F Regal; Megan E Strehlke; Jenna M Peterson; Cameron R Wing; Jordan E Parker; Noel Fernando Nieto; Lynne T Bemis; Jeffrey S Gilbert; Sherry D Fleming Journal: Mol Immunol Date: 2016-08-30 Impact factor: 4.407
Authors: Mimi Y Kim; Jill P Buyon; Marta M Guerra; Sarosh Rana; Dongsheng Zhang; Carl A Laskin; Michelle Petri; Michael D Lockshin; Lisa R Sammaritano; D Ware Branch; T Flint Porter; Joan T Merrill; Mary D Stephenson; Qi Gao; S Ananth Karumanchi; Jane E Salmon Journal: Am J Obstet Gynecol Date: 2015-09-29 Impact factor: 8.661
Authors: Tracey L Weissgerber; Augustine Rajakumar; Ashley C Myerski; Lia R Edmunds; Robert W Powers; James M Roberts; Robin E Gandley; Carl A Hubel Journal: J Clin Endocrinol Metab Date: 2013-12-11 Impact factor: 5.958
Authors: Kathryn E Lillegard; Alex C Johnson; Sarah J Lojovich; Ashley J Bauer; Henry C Marsh; Jeffrey S Gilbert; Jean F Regal Journal: Mol Immunol Date: 2013-05-15 Impact factor: 4.407