Cytokines atherosclerosis

Lutgens E, Faber B, Schapira K, et al. Gene profiling in atherosclerosis reveals a key role for small inducible cytokines validation using a novel monocyte chemoattractant protein monoclonal antibody. Circulation 2005 111(25) 3443-3452. 

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]. 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

Sterol carrier protein 2 has also been shown to be involved in the intracellular transport and metabolism of cholesterol. Hirai et al. (1994) suggested that sterol carrier protein 2 plays an important role during foam cell formation induced by acetylated LDL and may be an important step in atherosclerosis [142], Lipoproteins can bind lipopolysaccharide and decrease the lipopoly-saccharide-stimulated production of proinflammatory cytokines [142, 143], In addition, lipoprotein entrapment by the extracellular matrix can lead to the progressive oxidation of LDL because of the action of lipoxygenases, reactive oxygen species, peroxynitrite, or myeloperoxidase [144, 145],... 

Kaul D. Molecular link between cholesterol, cytokines and atherosclerosis. Mol Cell Biochem 2001 219 65-71. 

However, apart from disease states, there is a natural evolution of cytokine production with aging, including decreased T cell proinflammatory IL-2 and interferon-7 (type II pro-inflammatory IFN-7), decreased non-T cell antiinflammatory type I IFN (IFN-a and IFN-/3), and increased non-T cell proinflammatory IL-1, IL-6, and tumor necrosis factor a (TNF-o) [90], The IL-6 is one of the pathogenic elements of inflammatory and age-related diseases (AD and atherosclerosis) and has been defined as the cytokine for gerontologists [91]. 

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