scholarly journals Vascular Adhesion Protein-1 Determines the Cellular Properties of Endometrial Pericytes

2021 ◽  
Vol 8 ◽  
Author(s):  
Seley Gharanei ◽  
Katherine Fishwick ◽  
Ruban Peter Durairaj ◽  
Tianrong Jin ◽  
Eleftherios Siamantouras ◽  
...  
Keyword(s):  
Functional Properties ◽  
Immune Cell ◽  
Amine Oxidase ◽  
Killer Cell ◽  
Human Endometrium ◽  
Cell Trafficking ◽  
Adhesion Protein ◽  
Potential Biomarker ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule and a primary amine oxidase involved in immune cell trafficking. Leukocyte extravasation into tissues is mediated by adhesion molecules expressed on endothelial cells and pericytes. Pericytes play a major role in the angiogenesis and vascularization of cycling endometrium. However, the functional properties of pericytes in the human endometrium are not known. Here we show that pericytes surrounding the spiral arterioles in midluteal human endometrium constitutively express VAP-1. We first characterize these pericytes and demonstrate that knockdown of VAP-1 perturbed their biophysical properties and compromised their contractile, migratory, adhesive and clonogenic capacities. Furthermore, we show that loss of VAP-1 disrupts pericyte-uterine natural killer cell interactions in vitro. Taken together, the data not only reveal that endometrial pericytes represent a cell population with distinct biophysical and functional properties but also suggest a pivotal role for VAP-1 in regulating the recruitment of innate immune cells in human endometrium. We posit that VAP-1 could serve as a potential biomarker for pregnancy pathologies caused by a compromised perivascular environment prior to conception.

Bioluminescent Method for Assaying Multiple Semicarbazide-Sensitive Amine Oxidase (SSAO) Family Members in Both 96- and 384-Well Formats

2011 ◽  
Vol 16 (9) ◽  
pp. 1106-1111 ◽  
Author(s):  
Gregory W. Peet ◽  
Susan Lukas ◽  
Melissa Hill-Drzewi ◽  
Leslie Martin ◽  
Irina V. Rybina ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Immune Cell ◽  
Amine Oxidase ◽  
Inflammatory Diseases ◽  
Live Cells ◽  
Primary Amines ◽  
Cell Trafficking ◽  
Vascular Adhesion

Vascular adhesion protein–1 (VAP-1), also known as semicarbazide-sensitive amine oxidase (SSAO) or copper-containing amine oxidase (AOC3, EC 1.4.3.6), catalyzes oxidative deamination of primary amines. One endogenous substrate has recently been described (Siglec 10), and although its mechanism of action in vivo is not completely understood, it is suggested to play a role in immune cell trafficking, making it a target of interest for autoimmune and inflammatory diseases. Much of the enzymology performed around this target has been conducted with absorbance, fluorescent, or radiometric formats that can have some limitations for high-throughput screening and subsequent compound profiling. The authors present the use of a bioluminescent assay, originally developed for monoamine oxidase enzymes, in a high-throughput format. It can be used for related SSAOs such as AOC1 given their substrate similarity with VAP-1. The authors also demonstrate that it is compatible with different sources of VAP-1, both purified recombinant and VAP-1 overexpressed on live cells.

scholarly journals Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Activity Exerts an Antidiabetic Action in Goto-Kakizaki Rats

Diabetes ◽  
2003 ◽  
Vol 52 (4) ◽  
pp. 1004-1013 ◽  
Author(s):  
A. Abella ◽  
L. Marti ◽  
M. Camps ◽  
M. Claret ◽  
J. Fernandez-Alvarez ◽  
...  
Keyword(s):  
Amine Oxidase ◽  
Adhesion Protein ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

scholarly journals Semicarbazide-Sensitive Amine Oxidase/Vascular Adhesion Protein-1 Deficiency Reduces Leukocyte Infiltration into Adipose Tissue and Favors Fat Deposition

2009 ◽  
Vol 174 (3) ◽  
pp. 1075-1083 ◽  
Author(s):  
Sandy Bour ◽  
Sylvie Caspar-Bauguil ◽  
Zsuzsa Iffiú-Soltész ◽  
Maryse Nibbelink ◽  
Béatrice Cousin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amine Oxidase ◽  
Fat Deposition ◽  
Leukocyte Infiltration ◽  
Adhesion Protein ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

scholarly journals Vascular Adhesion Protein 1 in the Eye

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Wenting Luo ◽  
Fang Xie ◽  
Zhongyu Zhang ◽  
Dawei Sun
Keyword(s):  
Therapeutic Target ◽  
Amine Oxidase ◽  
Inflammatory Diseases ◽  
Age Related Macular Degeneration ◽  
Soluble Form ◽  
Dual Function ◽  
Ocular Diseases ◽  
Adhesion Protein ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1), a dual-function molecule with adhesive and enzymatic properties, is expressed on the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity and can be a prognostic biomarker. Recent evidence suggests that VAP-1 is an important therapeutic target for several inflammation-related ocular diseases, such as uveitis, age-related macular degeneration (AMD), and diabetic retinopathy (DR), by involving in the recruitment of leukocytes at sites of inflammation. Furthermore, VAP-1 plays an important role in the pathogenesis of conjunctival inflammatory diseases such as pyogenic granulomas and the progression of conjunctival lymphoma. VAP-1 may be an alternative therapeutic target in ocular diseases. The in vivo imaging of inflammation using VAP-1 as a target molecule is a novel approach with a potential for early detection and characterization of inflammatory diseases. This paper reviews the critical roles of VAP-1 in ophthalmological diseases which may provide a novel research direction or a potent therapeutic strategy.

scholarly journals Inhibition of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 reduces lipopolysaccharide-induced neuroinflammation

2017 ◽  
Vol 174 (14) ◽  
pp. 2302-2317 ◽  
Author(s):  
Serena Becchi ◽  
Alberto Buson ◽  
Jonathan Foot ◽  
Wolfgang Jarolimek ◽  
Bernard W Balleine
Keyword(s):  
Amine Oxidase ◽  
Adhesion Protein ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

scholarly journals Comparison of Inhibitor and Substrate Selectivity between Rodent and Human Vascular Adhesion Protein-1

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ryo Kubota ◽  
Michael J. Reid ◽  
Kuo Lee Lieu ◽  
Mark Orme ◽  
Christine Diamond ◽  
...  
Keyword(s):  
Amine Oxidase ◽  
Leukocyte Adhesion ◽  
Primary Amines ◽  
Oxidative Deamination ◽  
Adhesion Protein ◽  
Common Marker ◽  
Small Primary ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that functions as a copper-containing amine oxidase and is involved in leukocyte adhesion at sites of inflammation. Inhibition of VAP-1 oxidative deamination has become an attractive target for anti-inflammatory therapy with demonstrated efficacy in rodent models of inflammation. A previous comparison of purified recombinant VAP-1 from mouse, rat, monkey, and human gene sequences predicted that rodent VAP-1 would have higher affinity for smaller hydrophilic substrates/inhibitors because of its narrower and more hydrophilic active site channel. An optimized in vitro oxidative deamination fluorescence assay with benzylamine (BA) was used to compare inhibition of five known inhibitors in recombinant mouse, rat, and human VAP-1. Human VAP-1 was more sensitive compared to rat or mouse VAP-1 (lowest IC50 concentration) to semicarbazide but was least sensitive to hydralazine and LJP-1207. Hydralazine had a lower IC50 in rats compared to humans, although not significant. However, the IC50 of hydralazine was significantly higher in the rat compared to mouse VAP-1. The larger hydrophobic compounds from Astellas (compound 35c) and Boehringer Ingelheim (PXS-4728A) were hypothesized to have higher binding affinity for human VAP-1 compared to rodent VAP-1 since the channel in human VAP-1 is larger and more hydrophobic than that in rodent VAP-1. Although the sensitivity of these two inhibitors was the lowest in the mouse enzyme, we found no significant differences between mouse, rat, and human VAP-1. Michaelis-Menten kinetics of the small primary amines phenylethylamine and tyramine were also compared to the common marker substrate BA demonstrating that BA had the highest affinity among the substrates. Rat VAP-1 had the highest affinity for all three substrates and mouse VAP-1 had intermediate affinity for BA and phenylethylamine, but tyramine was not a substrate for mouse VAP-1 under these assay conditions. These results suggest that comparing oxidative deamination in mouse and rat VAP-1 may be important if using these species for preclinical efficacy models.

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