Obesity of mice lacking VAP-1/SSAO by Aoc3 gene deletion is reproduced in mice expressing a mutated vascular adhesion protein-1 (VAP-1) devoid of amine oxidase activity

Author(s):  
Valentin Jargaud ◽  
Sandy Bour ◽  
François Tercé ◽  
Xavier Collet ◽  
Philippe Valet ◽  
...  
Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3388-3395 ◽  
Author(s):  
Kaisa Koskinen ◽  
Petri J. Vainio ◽  
David J. Smith ◽  
Marjo Pihlavisto ◽  
Seppo Ylä-Herttuala ◽  
...  

Abstract Polymorphonuclear leukocytes (PMNs) migrate from the blood into areas of inflammation by binding to the endothelial cells of blood vessels via adhesion molecules. Vascular adhesion protein-1 (VAP-1) is one of the molecules mediating leukocyte-endothelial cell interactions. It is also an endothelial cell-surface enzyme (amine oxidase) that produces reactive oxygen species during the catalytic reaction. To study the role of the enzymatic activity of VAP-1 in PMN extravasation, we used an enzymatically inactive VAP-1 mutant, specific amine oxidase inhibitors (including a novel small molecule compound), and anti-VAP-1 antibodies in several flow-dependent models. The enzyme inhibitors diminished PMN rolling on and transmigration through human endothelial cells under conditions of laminar shear stress in vitro. Notably, the enzyme inactivating point mutation abolished the capacity of VAP-1 to mediate transmigration. Moreover, the new VAP-1 inhibitor effectively prevented the extravasation of PMNs in an animal model of inflammation. These data show that the oxidase activity of VAP-1 controls PMN exit from the blood during the relatively poorly understood transmigration step. (Blood. 2004;103:3388-3395)


Diabetes ◽  
2003 ◽  
Vol 52 (4) ◽  
pp. 1004-1013 ◽  
Author(s):  
A. Abella ◽  
L. Marti ◽  
M. Camps ◽  
M. Claret ◽  
J. Fernandez-Alvarez ◽  
...  

2009 ◽  
Vol 174 (3) ◽  
pp. 1075-1083 ◽  
Author(s):  
Sandy Bour ◽  
Sylvie Caspar-Bauguil ◽  
Zsuzsa Iffiú-Soltész ◽  
Maryse Nibbelink ◽  
Béatrice Cousin ◽  
...  

Author(s):  
Seley Gharanei ◽  
Katherine Fishwick ◽  
Ruban Peter Durairaj ◽  
Tianrong Jin ◽  
Eleftherios Siamantouras ◽  
...  

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Wenting Luo ◽  
Fang Xie ◽  
Zhongyu Zhang ◽  
Dawei Sun

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.


2017 ◽  
Vol 174 (14) ◽  
pp. 2302-2317 ◽  
Author(s):  
Serena Becchi ◽  
Alberto Buson ◽  
Jonathan Foot ◽  
Wolfgang Jarolimek ◽  
Bernard W Balleine

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