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Vascular Adhesion (vascular + adhesion)
Selected AbstractsVascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patientsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2007A Madej Abstract Background, Vascular adhesion protein (VAP)-1 is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes. Objectives, The aim of this study was to investigate the expression of VAP-1 in the skin and serum of psoriatic patients. Material and methods, Seventy-one patients suffering from psoriasis aged between 23 and 89 years were included in the study. The mean psoriasis severity assessed according to the psoriasis area and severity index was 14.2 ± 9.6 points. The soluble VAP-1 serum concentration was evaluated by ELISA and VAP-1 expression in the skin (nine patients) immunohistochemically. Results, The serum concentration of soluble VAP-1 was significantly higher in psoriatic patients than in healthy controls (403.4 ± 130.8 ng/mL vs. 246.4 ± 68.0 ng/mL; P < 0.0001). No significant relationships were found between sVAP-1 concentration and studied clinical parameters, except the presence of pruritus. Mean number of VAP-1 positive vessels in psoriatic skin, both lesional (19.8 ± 1.4) and non-lesional (9.4 ± 1.4), was significantly higher than in healthy skin (5.4 ± 1.5; P < 0.005). Lesional psoriatic skin demonstrated significantly more VAP-1 positive vessels than non-lesional skin (P < 0.01). Conclusions, Significant overexpression of VAP-1 in both lesional and non-lesional psoriatic skin and higher serum level of soluble VAP-1 in psoriatic patients may indicate the role of VAP-1 in chronic inflammation occurring in psoriasis. However, because of lack of correlation between soluble VAP-1 serum levels and psoriasis severity this hypothesis needs further investigation. [source] Structure,Activity Relationships of SSAO/VAP-1 Arylalkylamine-Based SubstratesCHEMMEDCHEM, Issue 4 2009Francesc Yraola Dr. Abstract SSAO/VAP-1 substrates may be valuable for the treatment or prevention of diabetes mellitus, as they show insulin-mimetic properties. This review highlights the importance of studying the relevant steric and electronic features in the development of new ligands with better SSAO/VAP-1 recognition, enhanced selectivity over other amine oxidases, and improved metabolic behavior. Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) substrates show insulin-mimetic effects and are therefore potentially valuable molecules for the treatment of diabetes mellitus. Herein we review several structural and electronic aspects of SSAO arylalkylamine-based substrates. Two main modifications directly affect amine oxidase (AO) activity: 1),variation in ring substitution modulates the biological activity of the arylalkylamine ligand by converting a substrate into a substrate-like inhibitor, and 2),variation in the number of methylene units between the aromatic ring and the ammonium groups of the arylalkylamine substrates dramatically alters the oxidation rate between species. Furthermore, we review relevant information about mammalian SSAO/VAP-1 substrate selectivity and specificity over monoamine oxidases (MAOs). [source] Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations,,HUMAN MUTATION, Issue 8 2007Gila Idelman Abstract Multiple variants of the vascular adhesion molecule-1 (VCAM1) promoter show increased nucleotide heterozygosity in the African American population. Using a novel transfection-based transcriptional pathway profiling method, we show that select uncommon variants are functionally hyperactive. Eight candidate VCAM1 promoter haplotypes comprising 13 previously identified SNPs were assessed for response to known mitogens. Activity was correlated with bioinformatic analysis of hyper- and hyporesponsive variants to identify the gain or loss of haplotype-specific transcription factor binding site (TFBS). Using this approach, a low frequency regulatory allele (c.,540A>G; dbSNP rs3783605:A>G), found in a hyperactive VCAM1 promoter haplotype, was shown to create a candidate binding site for ETS2 that was confirmed in vivo by chromatin immunoprecipitation. This report provides the first functional evaluation of VCAM1 promoter polymorphisms and establishes a hypothetical foundation for investigation of their role in the pathogenesis of VCAM1 -associated diseases that disproportionately afflict African Americans, including thromboembolic diseases, asthma, and multiple myeloma. Hum Mutat 28(8), 824,829, 2007. Published 2007, Wiley-Liss, Inc. [source] Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2003Alan J. Thomas Abstract Background Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Methods We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n,=,20) and control (n,=,20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). Results We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p,=,0.01) and a trend towards an increase for VCAM-1 (p,=,0.10). In the gyral white matter there was a trend towards significance for both molecules (p,=,0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. Conclusions These findings are consistent with white matter ischemia in the DLPFC and lend support to the ,vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future. Copyright © 2002 John Wiley & Sons, Ltd. [source] Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-,-treated human aortic endothelial cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2001Yung-Hsiang Chen Abstract Attachment to, and migration of leukocytes into the vessel wall is an early event in atherogenesis. Expression of cell adhesion molecules by the arterial endothelium may play a major role in atherosclerosis. It has been suggested that antioxidants inhibit the expression of adhesion molecules and may thus attenuate the processes leading to atherosclerosis. In the present study, the effects of a potent water-soluble antioxidant, salvianolic acid B (Sal B), and an aqueous ethanolic extract (SME), both derived from a Chinese herb, Salvia miltiorrhiza, on the expression of endothelial-leukocyte adhesion molecules by tumor necrosis factor-, (TNF-,)-treated human aortic endothelial cells (HAECs) were investigated. When pretreated with SME (50 and 100 ,g/ml), the TNF-,-induced expression of vascular adhesion molecule-1 (VCAM-1) was notably attenuated (77.2,±,3.2% and 80.0,±,2.2%, respectively); and with Sal B (1, 2.5, 5, 10, and 20 ,g/ml), 84.5,±,1.9%, 78.8,±,1.2%, 58.9,±,0.4%, 58.7,±,0.9%, and 57.4,±,0.3%, respectively. Dose-dependent lowering of expression of intercellular cell adhesion molecule-1 (ICAM-1) was also seen with SME or Sal B. In contrast, the expression of endothelial cell selectin (E-selectin) was not affected. SME (50 ,g/ml) or Sal B (5 ,g/ml) significantly reduced the binding of the human monocytic cell line, U937, to TNF-,-stimulated HAECs (45.7,±,2.5% and 55.8,±,1.2%, respectively). SME or Sal B significantly inhibited TNF-,-induced activation of nuclear factor kappa B (NF-,B) in HAECs (0.36- and 0.48-fold, respectively). These results demonstrate that SME and Sal B have anti-inflammatory properties and may explain their anti-atherosclerotic properties. This new mechanism of action of Sal B and SME, in addition to their previously reported inhibition of LDL, may help explain their efficacy in the treatment of atherosclerosis. J. Cell. Biochem. 82:512,521, 2001. © 2001 Wiley-Liss, Inc. [source] Crystallization and preliminary X-ray analysis of the human vascular adhesion protein-1ACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2003Yvonne Nymalm Human vascular adhesion protein-1 (VAP-1) is a membrane-bound multifunctional glycoprotein with both adhesive and enzymatic properties. The protein belongs to the copper-containing amine oxidase (CAO) family, which use 2,4,5-trihydroxyphenylalanine quinone as a cofactor. Here, the crystallization and preliminary X-ray analysis of a mammalian CAO, human VAP-1, is reported. The protein was expressed in Chinese hamster ovary cells as a full-length form with an N-terminal transmembrane region and multiple glycosylation sites. Hexagonal crystals with unit-cell parameters a = b = 225.9, c = 218.7,Å, , = , = 90, , = 120° were obtained using the vapour-diffusion method. Data from three different crystals were collected at 100,K using synchrotron radiation and were processed to 3.2,Å resolution with 95.9% completeness and an Rmerge of 19.6%. [source] | ||||||||||||||||