Vascular cell adhesion molecules

A 3D model of the fibrinogen-derived (very late antigen-4, VLA-4) inhibitor 4-[N -(2-methylphenyl)ureido]phenylacetyl-Leu-Asp-Val was derived from the X-ray structure of the related integrin-binding region of the vascular cell adhesion molecule-1 (VCAM-1). A 3D pharmacophore was generated with the program Catalyst, and a 3D search was performed in 8624 molecules from... 

IkB inhibitory protein kappa B lCAM-1 intercellular adhesion molecule 1 lL-1 interleukin-1 LDL low density lipoprotein MAPKs mitogen activated protein kinases MCP-1 macrophage chemotactic protein 1 M-CSF macrophage colony stimulating factor mmLDL minimally modified LDL NAC A-acetylcysteine NF-kB nuclear factor-kappa B oxLDL oxidised LDL PKC protein kinase C PMA phobol myristate acetate ROS reactive oxygen species TNF-a tumour necrosis factor alpha AM-1 vascular cell adhesion molecule 1... 

Selective inhibition of tumor necrosis factor-induced vascular cell adhesion molecule-1 gene expression by a novel flavonoid. Lack of effect on trascriptional factor NF-kB Arteriosclerosis, Thrombosis and Vascular Biology 16, 1501-8. 

NF-xB activates genes encoding MHC class I antigens, IL-1, TNFa, IL-6, the interleukin-2 (IL-2) receptor, some acute-phase proteins and the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) (lademarco... 

Mazo IB, Gutienez-Ramos JC, Frenette PS, Hynes RO, Wagner DD, von Andrian UH. Hematopoietic progenitor cell rolling in bone marrow microvessels parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J Exp Med 1998 188(3) 465-474. 

Frenette PS, Subbarao S, Mazo IB, von Andrian UH, Wagner DD. Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proc Natl Acad Sci U S A 1998 95(24) 14423-14428. 

Simmons PJ, Masinovsky B, Longenecker BM, Berenson R, Torok-Storb B, Gallatin WM. Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells. Blood 1992 80(2) 388—395. 

C8. Carlos, T Swartz, R Kovach, N. L., Yee, E., Rosso, M., Osbom, L. C Rosso, G., Newman, B Lobb, R., and Harlan, J., Vascular cell adhesion molecule-1 (VCAM-1) mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 76, 965-970 (1990). 

Haraldsen, G., Kvale, D., Lien, B., Farstad, I.N. and Brandtzaeg, P. (1996) Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (IGAM-1), and vascular cell adhesion molecule-1 (VGAM-1) in human microvascular endothelial cells. Journal of Immunology 156, 2558-2565. 

Halichlorine 11 is a structurally unique alkaloid that was isolated from the sponge Halichondria okadai and found to act as an inhibitor of the induction of vascular cell adhesion molecule (VCAM-1), a potential target in the development of drugs for the treatment of several vascular diseases. The strategies employed for the construction of its spiroquinolizidine unit are summarized in Scheme 106. 

Wang-Polagruto JF, Villablanca AC, Polagruto JA, Lee L, Holt RR, Schrader HR, Ensunsa JL, Steinberg FM, Schmitz HH and Keen CL. 2006. Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women. J Cardiovasc Pharmacol 47 Suppl 2 S177-186 discussion S206-209. 

Simoncini T, De Caterina R, Genazzani AR (1999) Selective estrogen receptor modulators different actions on vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J Clin Endocrinol Metab 84 815-818... 

Natalizumab (Tysabri ) is a recombinant humanized IgG4 mAb that binds to the a4-integrin subunit of a4(31 (VLA-4) and oA M (LPAM-1) integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the a4-mediated adhesion of leukocytes to their respective receptors.103 104 The receptor for a4pi, vascular cell adhesion molecule-1 (VCAM-1), is expressed on activated endothelial cells and is... 

VCAM-1 vascular cell adhesion molecule binds VLA-4... 

ICAM-1, ICAM-2) and vascular cell adhesion molecule (VCAM). Platelets are attracted to damaged endothelium where they adhere to prevent blood loss in a similar fashion to white blood cells, i.e. via adhesion molecule interactions, to form a clot (thrombus). 

SECs, like the vascular endothehum, play an active part in the control of leucocyte recruitment in cases of acute and chronic inflammatory conditions. Eeucocyte recruitment from the blood compartment is a crucial determinant for the induction of immunity and inflammation. SECs control this process by producing cytokines that activate leucocytes and by expressing adhesion molecules. Under inflammatory conditions upregulation of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was found [35 36], as well as expression of E-selectin and P-selectin [37]. Together with the expression of CD4 on SECs it has been postulated that these adhesion molecules might also be involved in the adhesion of KC cells to the sinusoidal wall [20]. 

Cyclic peptide inhibitors of VLA-1 and fibronectin/vascular cell adhesion molecule... 

Elevated concentrations of TNF have been found in the joints of RA patients and the stools of Crohn disease patients and correlate with elevated disease activity. In Crohn disease, infliximab reduces infiltration of inflammatory cells and TNF production in inflamed areas of the intestine and reduces the proportion of mononuclear cells from the lamina propria able to express TNF and interferon. In RA, treatment with infliximab reduced infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules mediating cellular adhesion and vascular cell adhesion molecule-1, chemoattraction, and tissue degradation. After treatment with infliximab, patients with Crohn disease or RA have decreased levels of serum IL-6 and C-reactive protein compared with baseline. 

Halichlorine (1) (Fig. 11.1) is an alkaloid which was isolated from the marine sponge H. okadai Kadota (Kuramoto et ah, 1996). This compound was revealed to be a novel alkaloid containing an azaspiro[4.5]decane skeleton clarified by detailed spectroscopic analyses. The absolute stereostructure was confirmed by many synthetic studies (Arimoto et ah, 1998 Clive et ah, 2005 Liu et ah, 2009 Trauner et ah, 1999). Halichlorine was shown to inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1) in cultured human umbilical vein endothelial cells. Drugs that block the inflammatory stimuli-induced expression of VCAM-1 may be useful for treating atherosclerosis, coronary artery diseases, angina, and noncardiovascular inflammatory diseases (Kock et ah, 1995). We introduce here the recent aspects of the biological and physiological activities of halichlorine. 

The quinolizidine alkaloid halichlorine (203), isolated from the marine sponge Halichondria okadai, inhibits the induction of vascular cell adhesion molecule-1 (VCAM-1) at IC50 7 pg/ml, which may be useful for treating atherosclerosis, coronary artery diseases, angina and noncardiovascular inflammatory diseases [161]. 

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