Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A vascular endothelial growth factor (VEGF) mRNA species containing exons 1-6 and 8 of the VEGF gene was found to be expressed as a major VEGF mRNA form in several cell lines derived from carcinomas of the female reproductive system. This mRNA is predicted to encode a VEGF form of 145 amino acids (VEGF145). Recombinant VEGF145 induced the proliferation of vascular endothelial cells and promoted angiogenesis in vivo. VEGF145 was compared with previously characterized VEGF species with respect to interaction with heparin-like molecules, cellular distribution, VEGF receptor recognition, and extracellular matrix (ECM) binding ability. VEGF145 shares with VEGF165 the ability to bind to the KDR/flk-1 receptor of endothelial cells. It also binds to heparin with an affinity similar to that of VEGF165. However, VEGF145 does not bind to two additional endothelial cell surface receptors that are recognized by VEGF165 but not by VEGF121. VEGF145 is secreted from producing cells as are VEGF121 and VEGF165. However, VEGF121 and VEGF165 do not bind to the ECM produced by corneal endothelial cells, whereas VEGF145 binds efficiently to this ECM. Basic fibroblast growth factor (bFGF)-depleted ECM containing bound VEGF145 induces proliferation of endothelial cells, indicating that the bound VEGF145 is active. The mechanism by which VEGF145 binds to the ECM differs from that of bFGF. Digestion of the ECM by heparinase inhibited the binding of bFGF to the ECM and released prebound bFGF, whereas the binding of VEGF145 was not affected by heparinase digestion. It therefore seems that VEGF145 possesses a unique combination of biological properties distinct from those of previously characterized VEGF species.
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PMID:VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. 905 10

Exposure of animals to hyperoxia decreases lung VEGF mRNA expression concomitant with an acute increase in VEGF protein within the epithelial lining fluid (ELF). The VEGF concentration in ELF is in excess of that found in the plasma, leading to the hypothesis that hyperoxia stimulates the release of VEGF protein from stores within the extracellular matrix. To test this hypothesis in a cell culture system, we exposed A549 cells to 95% O(2) (Ox) for 48 h followed by recovery in room air (RA) for 24 h. We found that Ox increased VEGF protein two- to threefold within the medium at 48 h of exposure and during recovery. Heparin clearing revealed the medium to contain a 50/50 mixture of the heparin-binding (VEGF(165)) and heparin-nonbinding (VEGF(121)) proteins and that Ox increased both proteins equally. Transcriptional activation of VEGF seems unlikely to explain the increase in VEGF protein, as expression of full-length and splice variant VEGF mRNA was unchanged by hyperoxia. Analysis of cell-associated VEGF proteins found that Ox increased the expression of VEGF(121) and VEGF(165) proteins. Blocking binding sites with exogenous heparin enhanced VEGF protein in the medium from RA-grown cells, whereas heparinase digestion of bound VEGF revealed a greater reserve of VEGF protein in RA cells. Collectively these findings indicate that hyperoxia enhances the expression of VEGF(121/165) proteins and facilitates the release of VEGF(165) from cell-associated stores. Increases in VEGF in ELF may represent an adaptive response fostering cell survival and type II cell proliferation in O(2)-induced lung injury.
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PMID:Hyperoxia enhances VEGF release from A549 cells via post-transcriptional processes. 1766 48

VEGF was first described as vascular permeability factor, a potent inducer of vascular leakage. Genetic evidence indicates that VEGF-stimulated endothelial proliferation in vitro and angiogenesis in vivo depend on heparan sulfate, but a requirement for heparan sulfate in vascular hyperpermeability has not been explored. Here we show that altering endothelial cell heparan sulfate biosynthesis in vivo decreases hyperpermeability induced by both VEGF(165) and VEGF(121). Because VEGF(121) does not bind heparan sulfate, the requirement for heparan sulfate suggested that it interacted with VEGF receptors rather than the ligand. By applying proximity ligation assays to primary brain endothelial cells, we show a direct interaction in situ between heparan sulfate and the VEGF receptor, VEGFR2. Furthermore, the number of heparan sulfate-VEGFR2 complexes increased in response to both VEGF(165) and VEGF(121). Genetic or heparin lyase-mediated alteration of endothelial heparan sulfate attenuated phosphorylation of VEGFR2 in response to VEGF(165) and VEGF(121), suggesting that the functional VEGF receptor complex contains heparan sulfate. Pharmacological blockade of heparan sulfate-protein interactions inhibited hyperpermeability in vivo, suggesting heparan sulfate as a potential target for treating hyperpermeability associated with ischemic disease.
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PMID:Heparan sulfate regulates VEGF165- and VEGF121-mediated vascular hyperpermeability. 2097 61