Atherosclerotic proteins

The calcification of atherosclerotic plaques may be induced by osteopontin expression, since osteopontin is a protein with a well-characterized role in bone formation and calcification. Vascular smooth muscle cell migration on osteopontin is dq endent on the integrin av 33 and antagonists of av 33 prevent both smooth muscle cell migration and restenosis in some animal model [8]. 

Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupmre of an atherosclerotic plaque). These processes encompass blood clotting (coagulation) and involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates. 

Yla-Herttuala, S., Rosenfeld, M.E., Parthasarathy, S., Glass, C.R., Sigal, E., Witztum, J.L. and Steinberg, D. (1990). Colocalisation of 15-lipoxygenase messenger RNA and protein with epitopes of oxidised low density lipoprotein in macrophage-rich areas of atherosclerotic lesion. Proc. Natl Acad. Sci. USA, 87, 6959-6963. 

Rus HG, Vlaicu R, Niculescu F. Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis 1996 127(2) 263-271. 

Huo Y, Weber C, Forlow SB, et al. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium. J Clin Invest 2001 108(9) 1307-1314. 

J8. Johnson, A. D Berberian, P. A., and Bond, M. G Effect of heat shock proteins on survival of isolated aortic cells from normal and atherosclerotic cynomolgus macaques. Atherosclerosis 84, 111-119(1990). 

HOCl-mediated protein oxidation accelerates under pathophysiological conditions. Thus, proteins from extracellular matrix obtained from advanced human atherosclerotic lesions contained the enhanced levels of oxidized amino acids (DOPA and dityrosine) compared to healthy arterial tissue [44], It was also found that superoxide enhanced the prooxidant effect of hypochlorite in protein oxidation supposedly by the decomposition of chloramines and chlor-amides forming nitrogen-centered free radicals and increasing protein fragmentation [45], In addition to chlorination, hypochlorite is able to oxidize proteins. The most readily oxidized amino acid residue of protein is methionine. Methionine is reversibly oxidized by many oxidants including hypochlorite to methionine sulfide and irreversibly to methionine sulfone [46] ... 

JTT-705 (17) is an irreversible inhibitor of CETP (IC50 = 6 (iM) and is believed to affect the function of CETP protein by binding to its Cys13 residue. In rabbits, 17 dose-dependently reduced CETP activity, raised HDL and reduced atherosclerotic lesions [75]. The results from Phase-II clinical trials on 17 show good HDL elevation (26-37% at 600-900 mg/day) during 4 weeks of treatment [64,76-78]. Compound 17 is also reported to lack hypertensive effects. 

Kockx, M.M., De Meyer, G.R., Muhiing, J., Jacob, W., Bull, H., and Herman, A.G.., 1998fc, Apoptosis and related proteins in different stages ofhuman atherosclerotic plaques. Circulation 97 2307-2315. 

Fuhrman, B., M. Rosenblat, T. Hayek, R. Coleman, and M. Aviram. Ginger extract consumption reduces plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipo-protein E-deficient mice. J Nutr 2000 130(5) 1124-1131. 

Lower incidence of heart disease has also been reported in populations consuming large amounts of soy products. Lowering of cholesterol is probably the best-documented cardioprotective effect of soy. ° Soy protein incorporated into a low-fat diet can reduce cholesterol and LDL-cholesterol concentrations and the soy isoflavones are likely to contribute to these effects. Soy isoflavones have been reported to improve cardiovascular risk factors in peripubertal rhesus monkeys, and inflammatory markers in atherosclerotic, ovariecto-mized monkeys. The potential role of phytoestrogens, including isoflavonoids, as cardioprotective agents has been extensively reviewed." ... 

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