Vascular Adhesion Protein-1: A Cell Surface Amine Oxidase in Translation

• Published in: Antioxidants & redox signaling Vol. 30; no. 3; p. 314
• Main Authors: Salmi, Marko, Jalkanen, Sirpa
• Format: Journal Article
• Language: English
• Published: United States 20.01.2019
• Subjects: Amine Oxidase (Copper-Containing) - antagonists & inhibitors; Amine Oxidase (Copper-Containing) - chemistry; Amine Oxidase (Copper-Containing) - metabolism; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - metabolism; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Surface Properties; cancer; inflammation; leukocyte trafficking; hydrogen peroxide
• ISSN: 1557-7716
• DOI: 10.1089/ars.2017.7418

Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that oxidates primary amines in a reaction producing also hydrogen peroxide. VAP-1 on the blood vessel endothelium regulates leukocyte extravasation from the blood into tissues under physiological and pathological conditions. Inhibition of VAP-1 by neutralizing antibodies and by several novel small-molecule enzyme inhibitors interferes with leukocyte trafficking and alleviates inflammation in many experimental models. Targeting of VAP-1 also shows beneficial effects in several other diseases, such as ischemia/reperfusion, fibrosis, and cancer. Moreover, soluble VAP-1 levels may serve as a new prognostic biomarker in selected diseases. Understanding the contribution of the enzyme activity-independent and enzyme activity-dependent functions, which often appear to be mediated by the hydrogen peroxide production, in the VAP-1 biology will be crucial. Similarly, there is a pressing need to understand which of the VAP-1 functions are regulated through the modulation of leukocyte trafficking, and what is the role of VAP-1 synthesized in adipose and smooth muscle cells. The specificity and selectivity of new VAP-1 inhibitors, and their value in animal models under therapeutic settings need to be addressed. Results from several programs studying the therapeutic potential of VAP-1 inhibition, which now are in clinical trials, will reveal the relevance of this amine oxidase in humans.