Atherosclerosis events induced

As described above, halichlorine was shown to inhibit LPS-induced events in BAECs, including adhesion-molecule expression, adherence of monocytes, and NF- activation. Thus, halichlorine is thought to be an attractive candidate for the adjunctive therapy of diseases such as atherosclerosis. 

Recent evidence suggests that atherosclerosis is a chronic inflammatory process. The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Alterations of chemotactic and adhesive properties of the endothelium play an important role in this process [82]. Quercetin has been reported to inhibit the expression in glomerular cells of monocyte chemoattractant protein-1 (MCP-1) [83] a potent chemoattractant for circulating monocytes. Red wine reduced MCP-1 mRNA and protein expression in abdominal aorta of cholesterol fed rabbits after balloon injury and this effect was associated with a reduced neointimal hyperplasia [84]. The antioxidant-mediated inhibition of nuclear factor k B (NFkB) and the subsequent non selective reduction of cytokine transcription have been suggested to be responsible for these effects [83]. Additionally, quercetin downregulated both phorbol 12-myristate 13-acetate (PMA)- and tumour necrosis factor-a (TNFa)-induced intercellular adhesion molecule-1 (ICAM-1) expression in human endothelial cells [86]. 

There is experimental evidence that suggests that some oxysterols, but not pure cholesterol, are the prime cause of atherosclerotic lesion formation (162). Upon cholesterol feeding, a strong relationship was seen between plasma oxysterols and aortic wall oxysterols. One may speculate that the deposition of pure lipids, such as cholesterol and its esters, may be merely a secondary process in response to oxysterol-induced endothelial cell injury. Cell injury/dysfunction and the subsequent disruption of endothelial barrier function by oxysterols (163, 164) could initiate the early events in atherosclerosis. Such injury could allow increased uptake... 

The response-to-injury hypothesis states that risk factors such as oxidized LDL, mechanical injury to the endothelium (e.g., percutaneous transluminal angioplasty), excessive homocysteine, immunologic attack, or infection-induced (e.g.. Chlamydia, herpes simplex virus 1) changes in endothelial and intimal function lead to endothelial dysfunction and a series of cellular interactions that culminate in atherosclerosis. C-reactive protein (CRP) is an acute-phase reactant and a marker for inflammation it may be useful in identifying patients at risk for developing CAD. The eventual outcomes of this atherogenic cascade are clinical events such as angina, MI, arrhythmias. 

Studies have shown that niacin significantly reduces ICAM-1, VCAM-1, PECAM and E-selectin levels. It also reduced the tumour necrosis (actor-alpha (TNF-a) induced rise in ICAM (it does this by reducing mRNA-induced expression of ICAM). It also decreased the production of ICAM through its reduction in interferon-y (IFN-y) and interleukin-1 (IL-l). Through these mechanisms, niacin induces a reduction of monocyte adhesion in endothelial cells This may possibly lead to decreased leucocyte adhesion to endothelium, which is an important early event in atherosclerosis (Tavintharan et al. 2009). 

Several studies have shown that the extent of coronary artery stenosis due to atherosclerotic plaque formation and expansion into the arterial lumen is not sufficient to explain the incidence of clinical events associated with atherosclerosis [183]. It appears that the generation of clinical events involves plaque mpture, resulting in thrombus formation and arterial occlusion. This mpture is induced by vasomotor disturbances in which oxidized low-density lipoproteins may be involved. Resveratrol is able to regulate vasomotion, which is impaired in atherosclerosis. The key regulators of the vasomotor function are the vasodilator NO and the vasoconstrictor endothelin-1 [167]. A number of in vitro and in vivo studies have shown improved vascular function in response to resveratrol [184, 185]. Resveratrol enhances expression and activity of endothelial nitric oxide synthase [186] and inhibits endothelin-1 secretion and endothelin-1 gene expression in human umbilical vein endothelial cells [187]. Intragastric administration of resveratrol for 12 weeks to hypercholesterolemic rabbits improved the endothelial function, reduced plasma endothelin-1 levels, and induced... 

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... 

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