The vascular endothelium acts as a selective barrier to regulate macromolecule exchange between the blood and tissues. However, the integrity of the endothelium barrier is compromised in an array of pathological settings, including ischemic disease and cancer, which are the leading causes of death worldwide. The resulting vascular hyperpermeability to plasma molecules as well as leukocytes then leads to tissue damaging edema formation and inflammation. The vascular endothelial growth factor A (VEGFA) is a potent permeability factor, and therefore a desirable target for impeding vascular hyperpermeability. However, VEGFA also promotes angiogenesis, the growth of new blood vessels, which is required for reperfusion of ischemic tissues. Moreover, edema increases interstitial pressure in poorly perfused tumors, thereby affecting the delivery of therapeutics, which could be counteracted by stimulating the growth of new functional blood vessels. Thus, targets must be identified to accurately modulate the barrier function of blood vessels without affecting angiogenesis, as well as to develop more effective pro‐ or anti‐angiogenic therapies. Recent studies have shown that the VEGFA co‐receptor neuropilin 1 (NRP1) could be playing a fundamental role in steering VEGFA‐induced responses of vascular endothelial cells towards angiogenesis or vascular permeability. Moreover, NRP1 is involved in mediating permeability signals induced by ligands other than VEGFA. This review therefore focuses on current knowledge on the role of NRP1 in the regulation of vascular permeability signaling in the endothelium to provide an up‐to‐date landscape of the current knowledge in this field.

Neuropilin 1 regulation of vascular permeability signaling / A. Domingues, A. Fantin. - In: BIOMOLECULES. - ISSN 2218-273X. - 11:5(2021 Apr 29), pp. 666.1-666.18. [10.3390/biom11050666]

Neuropilin 1 regulation of vascular permeability signaling

A. Domingues
Primo
;
A. Fantin
Ultimo
2021-04-29

Abstract

The vascular endothelium acts as a selective barrier to regulate macromolecule exchange between the blood and tissues. However, the integrity of the endothelium barrier is compromised in an array of pathological settings, including ischemic disease and cancer, which are the leading causes of death worldwide. The resulting vascular hyperpermeability to plasma molecules as well as leukocytes then leads to tissue damaging edema formation and inflammation. The vascular endothelial growth factor A (VEGFA) is a potent permeability factor, and therefore a desirable target for impeding vascular hyperpermeability. However, VEGFA also promotes angiogenesis, the growth of new blood vessels, which is required for reperfusion of ischemic tissues. Moreover, edema increases interstitial pressure in poorly perfused tumors, thereby affecting the delivery of therapeutics, which could be counteracted by stimulating the growth of new functional blood vessels. Thus, targets must be identified to accurately modulate the barrier function of blood vessels without affecting angiogenesis, as well as to develop more effective pro‐ or anti‐angiogenic therapies. Recent studies have shown that the VEGFA co‐receptor neuropilin 1 (NRP1) could be playing a fundamental role in steering VEGFA‐induced responses of vascular endothelial cells towards angiogenesis or vascular permeability. Moreover, NRP1 is involved in mediating permeability signals induced by ligands other than VEGFA. This review therefore focuses on current knowledge on the role of NRP1 in the regulation of vascular permeability signaling in the endothelium to provide an up‐to‐date landscape of the current knowledge in this field.
endothelium; neuropilin 1; permeability; semaphorin; VEGFA; animals; endothelium, vascular; gene expression regulation; humans; neuropilin-1; signal transduction; vascular endothelial growth factor A; capillary permeability
Settore BIO/09 - Fisiologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
biomolecules-11-00666-v2.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 1.76 MB
Formato Adobe PDF
1.76 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/878495
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 5
social impact