Vascular adhesion protein-1: Role in human pathology and application as a biomarker

Abstract

Vascular adhesion protein-1 (VAP-1) is a member of the copper-containing amine oxidase/semicarbazide-sensitive amine oxidase (AOC/SSAO) enzyme family. SSAO enzymes catalyze oxidative deamination of primary amines, which results in the production of the corresponding aldehyde, hydrogen peroxide and ammonium. VAP-1 is continuously expressed as a transmembrane glycoprotein in the vascular wall during development and facilitates the accumulation of inflammatory cells into the inflamed environment in concert with other leukocyte adhesion molecules. The soluble form of VAP-1 is released into the circulation mainly from vascular endothelial cells. Over- and under-expression of sVAP-1 result in alterations of the reported reaction product levels, which are involved in the pathogenesis of multiple human diseases. The combination of enzymatic and adhesion capacities as well as its strong association with inflammatory pathologies makes VAP-1 an interesting therapeutic target for drug discovery. In this article, we will review the general characteristics and biological functions of VAP-1, focusing on its important role as a prognostic biomarker in human pathologies. In addition, the potential therapeutic application of VAP-1 inhibitors will be discussed.

Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and activity of semicarbazide-sensitive amine oxidase

“…Thus, as expected, sVAP-1 and plasma SSAO activity showed tight correlation in our study. The membrane form of SSAO/VAP-1, highly expressed in endothelial cells, regulates leukocyte trafficking into site of inflammation (38). In obesity the membrane-bound VAP-1 is abundantly expressed on white fat cells, and is supposed to contribute to adipogenesis and pathological energy metabolism (38).…”

“…The membrane form of SSAO/VAP-1, highly expressed in endothelial cells, regulates leukocyte trafficking into site of inflammation (38). In obesity the membrane-bound VAP-1 is abundantly expressed on white fat cells, and is supposed to contribute to adipogenesis and pathological energy metabolism (38). It has been suggested that in obesity VAP-1 remains in the membrane-bound form, with a concurrent decrease in the circulating sVAP-1 concentration (39).…”

Theobromine and related methylxanthines as inhibitors of Primary Amine Oxidase

“…In the vascular endothelium, the extracellular domain may be cleaved off to give rise to a circulating form found in plasma. In some tissues, the membrane form acts as a Vascular Adhesion Protein (VAP‐1) which is involved in the migration of leukocytes through the vascular endothelium at sites of inflammation (Pannecoeck et al, ). This extravasion process requires the amine oxidase activity catalyzed by PrAO to be intact (Noonan, Lukas, Peet, & Pelletier, ).…”

“…Raised levels of PrAO are seen in a number of disease states including diabetes, Alzheimer's disease, and inflammation (Pannecoeck et al, ). The multiplicity of roles for PrAO in diverse processes has made it an important therapeutic target (O'Sullivan et al, ).…”

Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis

“…Although the roles of ICAM-1 and VCAM-1 during leukocyte transmigration in most vascular beds have been extensively studied (8)(9)(10), additional adhesion molecules have also been shown to partake in the transmigration process of encephalitogenic immune cells, including activated leukocyte cell adhesion molecule (ALCAM/CD166) (11,12), melanoma cell adhesion molecule (MCAM) (13)(14)(15), mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) (16,17), vascular adhesion protein (VAP-1) (18,19), Ninjurin-1 (20), and JAM-L (21). We have previously demonstrated that ALCAM is part of a group of adhesion molecules, found on BBB endothelial cells (BBB-ECs), that are involved in immune cell diapedesis (11,12).…”