Reduction of atherosclerosis

Teupser D, Pavlides S, Tan M, Gutierrez-Ramos JC, Kolbeck R, Breslow JL. Major reduction of atherosclerosis in fractalkine (CX3CLl)-deficient mice is at the brachiocephalic artery, not the aortic root. Proc Natl Acad Sci U S A 2004 101(51) 17795-1800. 

Wu, Y. J., C. Y. Hong, S. J. Lin, P. Wu, and M. S. Shiao. 1998. Increase of vitamin E content in LDL and reduction of atherosclerosis in cholesterol-fed rabbits by a water-soluble antioxidant-rich fraction of Salvia miltiorrhiza. Arterioscler. Thromb. Vase. Biol. 18 481-486. 

Optrin has demonstrated a reduction of atherosclerosis by eliminating inflammatory cells and is actually in Phase II studies for the primary treatment of peripheral artery disease and for the prevention of restenosis following angioplasty [71]. 

While much has been learned concerning predisposing conditions, it is quite possible that elimination or severe reduction of atherosclerosis awaits more fundamental findings as to the mechanism of atheromata formation situ. Plaque pathogenesis must occur at the molecular level in the vessel wall and very little is known regarding this phenomenon. 

Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998 394 200-203. 

Reduction in semm Hpids can contribute significantly to prevention of atherosclerosis. In 1985 a consensus report indicating that for every 1% reduction in semm cholesterol there is a 2% reduction in adverse effects of coronary heart disease was issued (145). Recommended semm cholesterol concentration was 200 mg/dL for individuals under 30 years of age, and individuals having concentration 240 mg/dL and LDL-cholesterol over 160 mg/dL should undertake dietary modification and possibly pharmacotherapy (146). Whereas the initial step in reducing semm cholesterol is through reduction of dietary cholesterol intake, a number of dmgs are available that can affect semm Hpid profile (see Fat substitutes). The pathway to cholesterol synthesis is shown in Figure 2. 

Cyanidin is the most common anthocyanin in foods. In addition, anthocyanins are stabilized by the formation of complexes with other flavonoids (co-pigmentation). In the United States, the daily anthocyanin consumption is estimated at about 200 mg. Several promising studies have reported that consumption of anthocyanin-rich foods is associated with reductions of the risks of cancers - and atherosclerosis and with preventive effects against age-related neuronal and behavioral declines. These beneficial effects of anthocyanins might be related to their reported biological actions such as modulators of immune response and as antioxidants. Knowledge of anthocyanin bioavailability and metabolism is thus essential to better understand their positive health effects. 

Based on the conventional understanding that CAD results from hyperlipidemia, atherosclerosis has been treated with good success by reduction of serum... 

Tangirala, RK, Pratico, D, FitzGerald, GA, Chun, S, Tsukamoto, K, Maugeais, C, Usher, DC, Pure, E, and Rader, DJ, 2001. Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J Biol Chem 276, 261-266. 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

W9. Watanabe, N., Yamada, S., Ishikawa, Y., and Yokoyama, M., Reduction of plasma lipopro-tein(a) by allelestrenol. Atherosclerosis (Shannon, Irel.) 102, 229-230 (1993). 

Reported rate constants for the reaction of 02 with GSH have varied from 102 to > 105 M 1 s. A re-examination of this reaction by spin trapping with DMPO established that earlier studies had been confounded by the direct reduction of the DMPO/ OOH adduct to DMPO/ OH by GSH. Taking account of this reaction, the revised rate constant was reported to be 200 M-1 g-i.25i.2S2 other workers have examined, for example, the effects of GSH and N-acetyl-L-cysteine on lipid peroxidation 253 and the role of GS in the toxicity of the diabetogenic agent alloxan.254 Direct EPR has been used to detect binuclear Cu(II) complexes of homocysteine. The interactions of such complexes with blood-vessel linings may account for the link between elevated homocysteine and atherosclerosis.255... 

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]. 

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