Vascular adhesion molecule 1 VCAM

Although reduction of plasmatic cholesterol and LDL is the major mechanism underlying the antiatherogenic actiOTi of OL and HT, additional effects are also involved. It is well established that local leukocyte and monocyte recruitment into the vessel wall is an early step in atherogenesis this event is correlated with the expression in the endothelial cells of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). OL and HT showed capacity to reduce LPS-stimulated expression of VCAM-1 in... 

The production of inflammatory cytokines and cell adhesion molecules (CAMs) by the arterial endothelium are key cellular events involved in the development of atherosclerosis. Activation of the endothelium results in the release of vascular cytokines such as interleukin-1 (IL-la) and tumor necrosis factor alpha (TNF-a). These cytokines induce the expression of CAMs such as intracellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), which, together with activated monocyte chemoattractant protein-1 (MCP-1), recruit monocytes through the vascular wall, where they are involved in foam cell formation. The nuclear transcription factor, NF-kB, is a mediator in TNF-a-induced expression of cell adhesion molecules and MCP. NF-kB is activated by an atherogenic diet (Liao et al. 1993) and oxidized LDL (Brand et al. 1997), and activation is inhibited by various antioxidants (Kunsch and Medford 1999). Therefore it is of particular interest that GEN attenuated NF-kB DNA binding and TNF-a release in human monocytes (Shames et al. 1999). A small, uncontrolled pilot study ( = 6) found that GEN, but not DAI, inhibited TNF-a-induced NF-kB activation in ex vivo human lymphocytes following consumption of 100 mg isoflavones/day for 3 weeks, as well as in cultured human... 

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. 

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). 

SPLA2, secretory phospholipase A2 COX-2, inducible nitric oxide synthase iNOS, inducible nitric oxide synthase SOD, superoxide dismutase ICAM-1, intracellular adhesion molecule-1 VCAM-1, vascular adhesion molecule-1 TNF-a, tumor necrosis factor-a IL, interleukin and MMP, matrix metalloproteinases. 

Fig. 8.1 A schematic diagram illustrating the involvement of NF-k I in gpl20, ROS, NO, PG, IL-1/3 and TNF-a-mediated neurotoxicity. NMDA-R, N-Methyl-D-aspartate receptor, cPLA2, cytosolic phospholipase A2 lyso-PtdCho, lysophosphatidylcholine AA, arachidonic acid cAMP, cyclic adenosine monophosphate PKA, protein kinase A TNF-a, tumor necrosis factor-a TNF-a-R, TNF-a-receptor IL-1/8, interleukin-1 /3 IL-l/i-R, IL-1/8-receptor, IL-6, interleukin-6 MARK, mitogen-activated protein kinase NO, nitric oxide PG, prostaglandins EP-R, prostaglandin receptors NF-kB, nuclear factor-icB NF-kB-RE, nuclear factor-/cB-response element I/cB, inhibitory subunit of NF-icB HIV-1, human immunodeficiency virus type 1 gpl20, HIV-1 coat glycoprotein COX-2, cyclooxygenase-2 iNOS, inducible nitric oxide synthase SPLA2, secretory phospholipase A2 SOD, superoxide dismutase MMP, matrix metalloproteinase and VCAM-1, vascular adhesion molecule-1...

Other groups have emphasized that previous infections are an independent risk factor for acute stroke. This phenomenon might be at least in part attributable to the activation of cytokines and adhesion molecules such as the vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) (5). 

Most of the IL-1 activity in plasma is from IL-lp, IL-la existing mainly in an intracellular or membrane-associated IL-1 shares many of its functions with TNF, but important differences between IL-1 and TNF exist. For example, IL-1 is in general not toxic, and TNF is a potent cytotoxic effector (see the Biological Actions of TNF section). One of their shared functions is the induction of expression of the vascular cell adhesion molecule (VCAM) by endothelial cells. Studies have indicated that TNF may be more important than IL-1 in induction of VCAM expression at least in the nasal mucosa. ... 

Rather than antagonising adhesion molecule expression on leucocytes, would it not be more advantageous to interfere with the expression of their counterreceptors on cerebral vessel walls It appears that endothelial cells adjacent to sites of infec-tion/inflammation in the CNS are just as likely to express increased levels of ICAM-1, VCAM-1, and P- and E-selectins as are similarly perturbed endothelial cells in other organs (e.g., skin, heart, and lung). Inhibiting the expression of these vascular adhesion molecules may impair lymphocyte trafficking across the BBB, but unfortunately it may also predispose to infection. 

Other members of the Ig-superfamily function in conjunction with counter-receptors from separate families of adhesion molecules in various events such as leukocyte trafficking and the movement of immune cells and probably tumor cells across cell barriers in inflammation and metastasis. These glycoproteins (Fig. 10) are the immune cell adhesion molecules ICAM-1, -2 and -3, the vascular cell adhesion molecule VCAM and the platelet-endothelial cell adhesion molecule PECAM [131-134]. 

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