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Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1

1
Istituto Dermopatico dell’Immacolata-IRCCS, 00167 Rome, Italy
2
Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University, 00185 Rome, Italy
3
National Research Council of Italy (CNR), Department of Biochemical Sciences “A. Rossi Fanelli”, Institute of Molecular Biology and Pathology c/o, Sapienza University, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1306; https://doi.org/10.3390/ijms19051306
Received: 10 April 2018 / Revised: 23 April 2018 / Accepted: 24 April 2018 / Published: 27 April 2018
(This article belongs to the Special Issue Vascular Endothelial Growth Factor)
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Abstract

Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling. In agreement with this activity, high levels of circulating sVEGFR-1 or sFlt1-14 are associated with different pathological conditions involving vascular dysfunction. Moreover, sVEGFR-1 and sFlt1-14 have an additional role in angiogenesis: they are deposited in the endothelial cell and pericyte extracellular matrix, and interact with cell membrane components. Interaction of sVEGFR-1 with α5β1 integrin on endothelial cell membranes regulates vessel growth, triggering a dynamic, pro-angiogenic phenotype. Interaction of sVEGFR-1/sFlt1-14 with cell membrane glycosphingolipids in lipid rafts controls kidney cell morphology and glomerular barrier functions. These cell–matrix contacts represent attractive novel targets for pharmacological intervention in addition to those addressing interactions between VEGFs and their receptors. View Full-Text
Keywords: Vascular endothelial growth factor receptor; angiogenesis; extracellular matrix Vascular endothelial growth factor receptor; angiogenesis; extracellular matrix
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Failla, C.M.; Carbo, M.; Morea, V. Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1. Int. J. Mol. Sci. 2018, 19, 1306.

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