scholarly journals Neuropilin 1 Regulation of Vascular Permeability Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 666
Author(s):  
Alison Domingues ◽  
Alessandro Fantin
Keyword(s):  
Blood Vessels ◽  
Vascular Permeability ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Vascular Endothelial ◽  
Edema Formation ◽  
Ischemic Disease ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

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.

scholarly journals Vascular Permeability Factor/Vascular Endothelial Growth Factor Induces Lymphangiogenesis as well as Angiogenesis

2002 ◽  
Vol 196 (11) ◽  
pp. 1497-1506 ◽  
Author(s):  
Janice A. Nagy ◽  
Eliza Vasile ◽  
Dian Feng ◽  
Christian Sundberg ◽  
Lawrence F. Brown ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Vessels ◽  
Vascular Permeability ◽  
Malignant Tumors ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Immunodeficient Mice ◽  
Permeability Factor ◽  
Endothelial Growth Factor

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A164, we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A–expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A164 also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new “giant” lymphatics generated by VEGF-A164 were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation.

scholarly journals VEGF-A in Cardiomyocytes and Heart Diseases

2020 ◽  
Vol 21 (15) ◽  
pp. 5294
Author(s):  
Mariantonia Braile ◽  
Simone Marcella ◽  
Leonardo Cristinziano ◽  
Maria Rosaria Galdiero ◽  
Luca Modestino ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Heart Diseases ◽  
Premature Death ◽  
Vascular Endothelial ◽  
Main Cell Type ◽  
High Concentrations ◽  
Cytokine Stimulation ◽  
The One ◽  
Endothelial Growth Factor

The vascular endothelial growth factor (VEGF), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis. Angiogenesis, the formation of new blood vessels, is responsible for a wide variety of physio/pathological processes, including cardiovascular diseases (CVD). Cardiomyocytes (CM), the main cell type present in the heart, are the source and target of VEGF-A and express its receptors, VEGFR1 and VEGFR2, on their cell surface. The relationship between VEGF-A and the heart is double-sided. On the one hand, VEGF-A activates CM, inducing morphogenesis, contractility and wound healing. On the other hand, VEGF-A is produced by CM during inflammation, mechanical stress and cytokine stimulation. Moreover, high concentrations of VEGF-A have been found in patients affected by different CVD, and are often correlated with an unfavorable prognosis and disease severity. In this review, we summarized the current knowledge about the expression and effects of VEGF-A on CM and the role of VEGF-A in CVD, which are the most important cause of disability and premature death worldwide. Based on clinical studies on angiogenesis therapy conducted to date, it is possible to think that the control of angiogenesis and VEGF-A can lead to better quality and span of life of patients with heart disease.

Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex

Angiogenesis ◽  
2014 ◽  
Vol 17 (4) ◽  
pp. 839-849 ◽  
Author(s):  
Ming-Heng Wu ◽  
Nien-Wen Ying ◽  
Tse-Ming Hong ◽  
Wei-Fan Chiang ◽  
Yueh-Te Lin ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

Role of connexin 43 in vascular hyperpermeability and relationship to Rock1-MLC20 pathway in septic rats

2015 ◽  
Vol 309 (11) ◽  
pp. L1323-L1332 ◽  
Author(s):  
Jie Zhang ◽  
Guang-ming Yang ◽  
Yu Zhu ◽  
Xiao-yong Peng ◽  
Tao Li ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Pulmonary Vein ◽  
Connexin 43 ◽  
Vascular Endothelial Cells ◽  
Pulmonary Veins ◽  
Cecal Ligation ◽  
Underlying Mechanism ◽  
Vascular Endothelial ◽  
Cx 43

Connexin (Cx)43 has been shown to participate in several cardiovascular diseases. Increased vascular permeability is a common and severe complication in sepsis or septic shock. Whether or not Cx43 takes part in the regulation of vascular permeability in severe sepsis is not known, and the underlying mechanism has not been described. With cecal ligation and puncture-induced sepsis in rats and lipopolysaccharide (LPS)-treated vascular endothelial cells (VECs) from pulmonary veins, the role of Cx43 in increased vascular permeability and its relationship to the RhoA/Rock1 pathway were studied. It was shown that vascular permeability in the lungs, kidneys, and mesentery in sepsis rats and LPS-stimulated monolayer pulmonary vein VECs was significantly increased and positively correlated with the increased expression of Cx43 and Rock1 in these organs and cultured pulmonary vein VECs. The connexin inhibitor carbenoxolone (10 mg/kg iv) and the Rock1 inhibitor Y-27632 (2 mg/kg iv) alleviated the vascular leakage of lung, mesentery, and kidney in sepsis rats. Overexpressed Cx43 increased the phosphorylation of 20-kDa myosin light chain (MLC20) and the expression of Rock1 and increased the vascular permeability and decreased the transendothelial electrical resistance of pulmonary vein VECs. Cx43 RNA interference decreased the phosphorylation of MLC20 and the expression of Rock1 and decreased LPS-stimulated hyperpermeability of cultured pulmonary vein VECs. The Rock1 inhibitor Y-27632 alleviated LPS- and overexpressed Cx43-induced hyperpermeability of monolayer pulmonary vein VECs. This report shows that Cx43 participates in the regulation of vascular permeability in sepsis and that the mechanism is related to the Rock1-MLC20 phosphorylation pathway.

scholarly journals Blockade of in vivo VEGF-mediated angiogenesis by antisense gene therapy: role of Flk-1 and Flt-1 receptors

2002 ◽  
Vol 282 (1) ◽  
pp. H194-H204 ◽  
Author(s):  
Geneviève S. Marchand ◽  
Nicolas Noiseux ◽  
Jean-François Tanguay ◽  
Martin G. Sirois
Keyword(s):  
Blood Vessels ◽  
Fetal Liver ◽  
Capillary Blood ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Antisense Gene ◽  
Endothelial Growth Factor ◽  
Phosphate Buffered Saline

Angiogenesis, the formation of new blood vessels from preexisting ones, is a critical component of various pathologies such as tumor progression, rheumatoid arthritis, and retinopathies. Vascular endothelial growth factor (VEGF) is a mitogenic and chimiotactic factor capable of inducing angiogenesis through the activation of its receptors, fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1), expressed on endothelial cells. The purpose of the present study was to assess if a treatment with antisense (AS) oligonucleotides directed against VEGF receptors Flk-1 or Flt-1 mRNA could prevent VEGF-mediated angiogenesis. With the use of miniosmotic pumps, phosphate-buffered saline, VEGF, or VEGF combined with AS-Flk-1, AS-Flt-1, or AS-scrambled oligonucleotides were released in mouse testis for 14 days. VEGF (1, 2.5, and 5 μg) increased the formation of new capillary blood vessels by 236, 246, and 287%, respectively. The combination of AS-Flk-1 or AS-Flt-1 (200 μg) to VEGF (2.5 μg) reduced by 87 and 85% the formation of new blood vessels, respectively, and the expression of their corresponding proteins. These data demonstrate the therapeutical potential of AS-Flk-1 or AS-Flt-1 to prevent VEGF-mediated angiogenesis in vivo.

scholarly journals Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute Hantavirus Pulmonary Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Irina Gavrilovskaya ◽  
Elena Gorbunova ◽  
Frederick Koster ◽  
Erich Mackow
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Pulmonary Edema ◽  
Vascular Permeability ◽  
Hantavirus Pulmonary Syndrome ◽  
Acute Pulmonary Edema ◽  
Vascular Endothelial ◽  
Edema Fluid ◽  
Endothelial Growth Factor

Hantavirus pulmonary syndrome is characterized by vascular permeability, hypoxia, and acute pulmonary edema. Vascular endothelial growth factor (VEGF) is induced by hypoxia, potently induces vascular permeability, and is associated with high-altitude-induced pulmonary edema. Hantaviruses alter the normal regulation ofβ3 integrins that restrict VEGF-directed permeability and hantavirus infected endothelial cells are hyperresponsive to the permeabilizing effects of VEGF. However, the role of VEGF in acute pulmonary edema observed in HPS patients remains unclear. Here we retrospectively evaluate VEGF levels in pulmonary edema fluid (PEF), plasma, sera, and PBMCs from 31 HPS patients. VEGF was elevated in HPS patients PEF compared to controls with the highest levels observed in PEF samples from a fatal HPS case. VEGF levels were highest in PBMC samples during the first five days of hospitalization and diminished during recovery. Significantly increased PEF and PBMC VEGF levels are consistent with acute pulmonary edema observed in HPS patients and HPS disease severity. We observed substantially lower VEGF levels in a severe HPS disease survivor after extracorporeal membrane oxygenation. These findings suggest the importance of patients’ VEGF levels during HPS, support the involvement of VEGF responses in HPS pathogenesis, and suggest targeting VEGF responses as a potential therapeutic approach.

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