Monocyte chemoattractant protein atherosclerosis

Gu L, Okada Y, Clinton SK, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 1998 2 275-81. 

Aiello RJ, Bourassa PA, Lindsey S, et al. Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vase Biol 1999 19(6) 1518-1525. 

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. 

Ni W, Egashira K, Kitamoto S, et al. New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice. Circulation 2001 103(16) 2096-2101. 

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]. 

P6. Peters, W., and Charo, I. F., Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis Lessons from knockout mice. Curr. Opin. Lipidol. 12, 175—180 (2001). 

Increases in plasma S-AA levels have previously been reported in patients with coronary disease (57). S-AA and plasma intracellular adhesion molecule-1 were elevated in patients with CAD and hyperhomocysteinemia, but only S-AA decreased after vitamin supplementation (35). Homocysteine activates nuclear factor- in endothelial cells, possibly via oxidative stress (58), and increases monocyte chemoattractant protein-1 expression in vascular smooth muscle cells (59). Additionally, it stimulates interleukin-8 expression in human endothelial cultures (60). These inflammatory factors are known to participate in the development of atherosclerosis. Taken together, these reports suggest an association of elevated tHcy and low-grade inflammation in CAD. 

Aiello, R. J., Bourassa, P. A., Lindsey, S., Weng, W., Natoli, E., Rollins, B.J., and Milos, P. M. (1999). Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb. Vase. Biol. 19, 1518-1525. 

Pasceri V, Chang J, Willerson PT, Yeh ETH. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001 103 2531-34. 

Gu, L., Okada, Y., Clinton, S. K., Gerard, C., Sukhova, G. K., Libby, P., and Rollins, B. J. (1998) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2,275-281... 

Inoue, S., Egashira, K., Ni, W., Kitamoto, S., Usui, M., Otani, K., Ishibashi, M., Hiasa, K., Nishida, K., and Takeshita, A. (2002). Anti-monocyte chemoattractant protein-1 gene therapy limits progression and destabilization of established atherosclerosis in apolipoprotein E-knockout mice. Circulation 106, 2700-2706. 

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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