Disease relevance of AOC3

• In conclusion insulin appears to regulate shedding or clearance of VAP-1, and an increase in sVAP-1 because of absolute or relative insulin deficiency may be directly involved in the pathogenesis of diabetic angiopathy [1].
• Together, these results suggest a role for SSAO-mediated deamination in pulmonary inflammation [2].
• The current study explored whether the changes in serum VAP-1 levels correlate with the changes in metabolic phenotypes after weight reduction surgery [3].
• Change in vascular adhesion protein-1 and metabolic phenotypes after vertical banded gastroplasty for morbid obesity [3].
• Expression of vascular adhesion protein-1 in atopic eczema [4].

Psychiatry related information on AOC3

• Our parsimonious conclusion is that there is a relation between the risk factors of AD and vascular dementia (diabetes, oxidative stress and chronic inflammation) and SSAO activity, which may originate from the vessel wall [5].
• We have previously reported that membrane-bound SSAO is overexpressed in the cerebrovascular tissue of Alzheimer's disease (AD) patients [6].
• SSAO activity was determined in plasma of control cases (n = 23) and patients suffering sporadic Alzheimer dementia, distributed according to the Global Deterioration Scale (GDS): mild (n = 33), moderate (n = 14), moderate-severe (n = 15) and severe dementia (n = 19) [6].

High impact information on AOC3

• We show here that catalytic activity of VAP-1 on primary endothelial cells directly regulates lymphocyte rolling under defined laminar shear [7].
• Vascular adhesion molecule-1 (VAP-1) is a surface-expressed endothelial glycoprotein, which belongs to a distinct subgroup of monoamine oxidases [7].
• We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain [8].
• Here we show that vascular adhesion protein-1 (VAP-1) mediates subtype-specific binding of CD8-positive T cells and natural killer cells to human endothelium [9].
• Finally, intravital microscopy revealed that VAP-1 is involved in initial interactions between human lymphocytes and endothelial cells in inflamed rabbit mesenterial venules in vivo [9].

Chemical compound and disease context of AOC3

• Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus [10].
• Aminoguanidine inhibits semicarbazide-sensitive amine oxidase activity: implications for advanced glycation and diabetic complications [11].
• These associations remained after adjusting for age, sex, glucose tolerance status, hypertension, prior cardiovascular disease, low-density lipoprotein cholesterol, homocysteine, (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1 and C-reactive protein [12].
• We examined the effects of VAP-1/SSAO inhibition [via LJP-1207 (N'-(2-phenyl-allyl)-hydrazine hydrochloride)] on pial venular leukocyte adhesion and infiltration (at 2-10 h of reperfusion) and neuropathology (at 72 h of reperfusion) after transient forebrain ischemia (TFI) [13].
• Vascular adhesion protein-1 plays an important role in postischemic inflammation and neuropathology in diabetic, estrogen-treated ovariectomized female rats subjected to transient forebrain ischemia [13].

Biological context of AOC3

• Our results demonstrated that the copper-binding motif and the enzyme active site of AOC1 and AOC3 were both conserved in mouse AOC2 [14].
• The presence of human and rat AOC pseudogene in this region, in addition to the tandemly positioned two AOC genes, indicates the possibility of successful AOC3 replication to retina-specific AOC2 for human and mouse but unsuccessful for rat [14].
• Vascular adhesion protein-1 (VAP-1) is one of the molecules mediating leukocyte-endothelial cell interactions [15].
• Notably, the enzyme inactivating point mutation abolished the capacity of VAP-1 to mediate transmigration [15].
• Serum VAP-1 might modulate DBP independently from the changes in insulin resistance in morbidly obese people [3].

Anatomical context of AOC3

• We undertook this study to determine the contribution of AOC3 and its oxidase activity to leukocyte trafficking into inflamed joints in vivo [16].
• Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind lymphocytes, and the binding can be partially inhibited with anti-VAP-1 mAbs [8].
• Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1) [15].
• These are the first studies to report the function of VAP-1 on primary human endothelial cells [17].
• Semicarbazide-sensitive amine oxidase (SSAO) resides on the vascular endothelium and smooth muscle cell surface and is capable of deaminating short chain aliphatic amines and producing toxic aldehydes and hydrogen peroxide [2].

Associations of AOC3 with chemical compounds

• The increase in SSAO activity observed in omental WAT likely results from an increased expression of the AOC3 gene since mRNA abundance and maximal benzylamine oxidation velocity were increased [18].
• The hepatic sinusoids are perfused by blood at low flow rates, and sinusoidal endothelium lacks selectin expression and has low levels of CD31, suggesting that VAP-1 may play a specific role in lymphocyte recruitment to the liver [17].
• DISCUSSION: The results suggest that VAP-1 levels are correlated with fasting glucose and insulin levels in morbidly obese subjects [3].
• The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding [19].
• In conclusion, VAP-1 naturally exists as a 170-kD sialoglycoprotein that uses sialic acid residues to interact with its counter-receptors on lymphocytes under nonstatic conditions [19].

Physical interactions of AOC3

• Vascular adhesion protein-1 and intercellular adhesion molecule-1 mediate T-cell binding to human hepatocellular carcinoma [20].

Regulatory relationships of AOC3

• However, PPAR-gamma activation significantly suppressed the expression of vascular adhesion molecules in ECs and the ensuing leukocyte recruitment [21].
• Transcription factors like STAT-1 and AP-1 are critically involved in this process by regulating vascular adhesion molecule expression [22].

Other interactions of AOC3

• Early features in the pathogenesis of atherosclerosis include accumulation of oxidized LDL (oxLDL) and endothelial expression of the vascular adhesion molecule VCAM-1 [23].
• Transcription factor nuclear factor kappa B (NF kappa B) controls gene expression of a number of genes including cell adhesion molecules such as E-selectin, intercellular adhesion molecule 1, and vascular adhesion molecule 1 [24].
• Using highly specific antisense oligonucleotides that target the mRNA encoding c-Raf kinase and Ha-Ras, we show here that inhibition of c-raf and Ha-ras expression blocks the up-regulation of E-selectin and vascular adhesion molecule-1 induced by TNFalpha in endothelial cells [25].
• On HLVEC, PGE1 down-regulated TNF-induced expression of endothelial cell leukocyte adhesion molecule 1 and vascular adhesion molecule 1, but not intercellular adhesion molecule 1 [26].
• In contrast, fewer T cells infiltrated CHM and these tumors have little ICAM-1 and no detectable VAP-1 or VCAM-1 on tumor endothelium [27].

Analytical, diagnostic and therapeutic context of AOC3

• Intraperitoneal and oral administration of the AOC3 inhibitor significantly ameliorated rat AIA [16].
• Moreover, the new VAP-1 inhibitor effectively prevented the extravasation of PMNs in an animal model of inflammation [15].
• RESEARCH METHODS AND PROCEDURES: Clinical characteristics and serum VAP-1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m(2)) were measured before and after vertical banded gastroplasty [3].
• The serum concentration of soluble VAP-1 (sVAP-1) was evaluated by ELISA and VAP-1 expression in the skin by immunohistochemistry [4].
• The 90-kD form of VAP-1 was only seen in an organ culture model, and may represent a monomeric or proteolytic form of the larger species [19].

References