Fig. 1: Biological roles and interaction of VAP-1 and MPO.

During inflammation, VAP-1 expressed on the luminal membrane of the activated endothelium facilitates the recruitment, adhesion and transmigration of leucocytes (e.g. neutrophils) into inflamed tissues, via its enzyme activity, which includes the local production of the redox signalling oxidant, hydrogen peroxide (H₂O₂). Recruited neutrophils release MPO in response to inflammatory stimuli, which upon activation by its co-substrate H₂O₂ (potentially derived from VAP-1 activity) catalyses a variety of oxidative reactions that result in the oxidation, chlorination and nitration of an array of biomolecules within the inflamed tissue (e.g. atherosclerotic lesion), leading to an inflammatory feedback loop, whereby additional leucocytes are recruited from the circulation. The inhibition of VAP-1 reduces leucocyte influx and the local generation of H₂O₂, leading to the reduced release of MPO. Inhibition of MPO reduces local oxidative tissue damage and inhibits the inflammatory feedback loop.