Neuropilin 1 Regulation of Vascular Permeability Signaling

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.

Coaxially Bioprinted Cell-Laden Tubular-Like Structure for Studying Glioma Angiogenesis

“…Our results showed that although U118-RFP and HUVEC-GFP weakly secreted bFGF, their bFGF secretability was remarkably enhanced when both types of cells were cocultured in hydrogel microfibers possibly because when tumor and endothelial cells were cocultured in a 3D microenvironment, the paracrine and autocrine pathways of the cells stimulated the ability of both cells to secrete vascular growth factors (Zhou et al, 2021). Several studies have demonstrated that vascular growth factors play an important role in angiogenesis (Domingues et al, 2021). As mentioned above, the 3D microenvironment composed of shell-U118-RFP/core-HUVEC-GFP was enriched in vascular growth factors.…”

The Anti-Colon Cancer Effects of Essential Oil of Curcuma phaeocaulis Through Tumour Vessel Normalisation

“…VEGFa is an important angiogenic factor. Its vascular permeability allows macromolecular proteins such as fibrinogen to leak from blood vessels, thereby forming capillary blood networks ( 5 ). Also, VEGFa selectively acts on vascular endothelial cells to promote proliferation and migration, to ultimately form new blood vessels ( 21 ).…”

“…At the cellular level, the vascular endothelium and pericytes in tumours are missing and cause serious leakage of vascular contents (2)(3)(4). This alteration exacerbates local hypoxia and acidosis in tumour environments, eventually converting tumour cells to malignant phenotypes and affecting the killing capacity of immune cells and therapeutics toward tumours (5).…”

Quantitative Assessment of the Apical and Basolateral Membrane Expression of VEGFR2 and NRP2 in VEGF-A-stimulated Cultured Human Umbilical Vein Endothelial Cells

“…19 Neuropilins have been shown to play a key role in vascular permeability, via binding to VEGF-A or to members of the semaphorin family. [20][21][22] Lack of NRP1 expression in mice reduces VEGF-A-induced vascular permeability, 20 whereas lack of NRP2 expression in mice increases inflammation-induced vascular permeability. 22 In the present study, we investigated how apical and/or basolateral VEGF-A stimulation regulates HUVEC barrier function.…”