Journal: Antioxidants & Redox Signaling

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

doi: 10.1089/ars.2017.7418

Figure Lengend Snippet: Crystallographic structure of VAP-1 . (A) Two identical monomers are colored blue and wheat . Copper (Cu) ion is orange and TPQ in each chain is presented as green spheres . (B) Docking of Siglec-9 peptide ( green ) into the active site of VAP-1. This binding mode is presented in Aalto et al. and assumes that the peptide binds covalently to TPQ. Courtesy of Dr. Tiina Salminen. Siglec, sialic acid-binding immunoglobulin-type lectins; TPQ, topaquinone; VAP-1, vascular adhesion protein-1.

Article Snippet: Astellas VAP-1 inhibitor (ASP8232) is in Phase II trial for diabetic macular edema in the United States and for diabetic nephropathy in Europe.

Techniques: Binding Assay

Journal: Antioxidants & Redox Signaling

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

doi: 10.1089/ars.2017.7418

Figure Lengend Snippet: VAP-1 is expressed in vascular endothelium and smooth muscle in human liver and tonsil. Triple stainings using anti-VAP-1, anti-smooth muscle actin (SMA), and anti-CD31 (pan-endothelial antibodies) are shown. Note that liver sinusoids ( arrowheads ) stain brightly with anti-VAP-1 but are devoid of smooth muscle present in larger vessels. Similarly, smaller capillaries are VAP-1/CD31 positive but lack SMA in tonsil ( arrows ).

Article Snippet: Astellas VAP-1 inhibitor (ASP8232) is in Phase II trial for diabetic macular edema in the United States and for diabetic nephropathy in Europe.

Techniques: Staining

Journal: Antioxidants & Redox Signaling

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

doi: 10.1089/ars.2017.7418

Figure Lengend Snippet: Functions of VAP-1 in health and disease. VAP-1 has multiple different physiological functions ( blue boxes ), and it is involved in their aberrations during different disease states ( yellow boxes ). Many of these processes are interdependent, and the role of VAP-1 in leukocyte extravasation is likely to contribute heavily to many of them.

Article Snippet: Astellas VAP-1 inhibitor (ASP8232) is in Phase II trial for diabetic macular edema in the United States and for diabetic nephropathy in Europe.

Techniques:

Journal: Antioxidants & Redox Signaling

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

doi: 10.1089/ars.2017.7418

Figure Lengend Snippet: A working model for VAP-1 function in the leukocyte extravasation cascade. A blood-borne leukocyte makes sequential contacts with the endothelial cell expressing VAP-1. When the two cell types (STEP 1) come in contact with each other (STEP 2) , a leukocyte counter-receptor of VAP-1 interacts in an enzyme activity-independent manner with the endothelial VAP-1. Thereafter, the same (or another) leukocyte surface molecule is used as a substrate in the VAP-1-mediated oxidative deamination reaction (STEP 3) . This results in the formation of a covalent but transient binding between the two cell types. After the catalytic reaction, the leukocyte surface molecule is modified into an aldehyde, a signaling molecule hydrogen peroxide is formed, and VAP-1 enzyme is converted back to the original state (STEP 4) . Note that the order of the proposed STEPs 2 and 3 is hypothetical.

Article Snippet: Astellas VAP-1 inhibitor (ASP8232) is in Phase II trial for diabetic macular edema in the United States and for diabetic nephropathy in Europe.

Techniques: Expressing, Activity Assay, Binding Assay, Modification

Journal: Antioxidants & Redox Signaling

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

doi: 10.1089/ars.2017.7418

Figure Lengend Snippet: VAP-1 can be used as a target for imaging. Representative sagittal ( left ), transaxial ( middle ), and coronal ( right ) multiplane PET images of [ 18 F]FDR-Siglec-9 (VAP-1 ligand) biodistribution in a rat. The images are summation from 10 to 60 min postinjection. Reproduced with permission from Chemical Communication [from Li et al. ].

Article Snippet: Astellas VAP-1 inhibitor (ASP8232) is in Phase II trial for diabetic macular edema in the United States and for diabetic nephropathy in Europe.

Techniques: Imaging