RATIONALE: The @entity7 ( @entity7 ) decoy receptor soluble @entity6758 (sVEGF-R1) is thought to protect the cells that produce it from adverse @entity7 signaling. To accomplish this role, a mechanism for pericellular retention of sVEGF-R1 is required. Local retention may also prevent the accumulation of high circulating levels of sVEGF-R1 and resulting interference with homeostatic @entity7 functions in remote organs. OBJECTIVE: To reveal natural storage depots of sVEGF-R1 and determine mechanisms underlying its pericellular retention. To uncover natural mechanisms regulating its systemic release. METHODS AND RESULTS: We show that both the canonical and @entity1 -specific isoforms of sVEGF-R1 are strongly bound to heparin. sVEGF-R1 produced by vascular smooth muscle cells is stored in the vessel wall and can be displaced from isolated @entity19 aorta by heparin. Another major reservoir of sVEGF-R1 is the placenta. Heparin increases the level of sVEGF-R1 released by cultured @entity1 placental villi, and pregnant @entity1 treated with low molecular weight heparin showed markedly elevated levels of sVEGF-R1 in the circulation. Heparanase is expressed in @entity1 placenta at the same locales as sVEGF-R1, and its transgenic overexpression in @entity19 resulted in a marked increase in the levels of circulating sVEGF-R1. Conversely, heparanase inhibition, by either a neutralizing antibody or by inhibition of its maturation, reduced the amounts of sVEGF-R1 released from @entity1 placental villi, indicating a natural role of heparanase in sVEGF-R1 release. CONCLUSIONS: Together, the findings uncover a new level of regulation governing sVEGF-R1 retention versus release and suggest that manipulations of the heparin/heparanase system could be harnessed for reducing unwarranted release of sVEGF-R1 in pathologies such as @entity1468 .

Local retention versus systemic release of soluble XXXX receptor-1 are mediated by heparin-binding and regulated by heparanase.

@entity1 :: ('9606', 'Species') :: ['women', 'human'] @entity7 :: ('7422', 'Gene') :: ['vascular endothelial growth factor', 'VEGF'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1468 :: ('MESH:D011225', 'Disease') :: ['preeclampsia'] @entity6758 :: ('2321', 'Gene') :: ['VEGF-R1']
@entity7 :: (7422,Gene) :: ['VEGF']
