Atherosclerosis Lecithin

FIGURE 9. Endogenous lipoprotein metabolism. In liver cells, cholesterol and triglycerides are packaged into VLDL particles and exported into blood where VLDL is converted to IDL. Intermediate-density lipoprotein can be either cleared by hepatic LDL receptors or further metabolized to LDL. LDL can be cleared by hepatic LDL receptors or can enter the arterial wall, contributing to atherosclerosis. Acetyl CoA, acetyl coenzyme A Apo, apolipoprotein C, cholesterol CE, cholesterol ester FA, fatty acid HL, hepatic lipase HMG CoA, 3-hydroxy-3-methyglutaryl coenzyme A IDL, intermediate-density lipoprotein LCAT, lecithin-cholesterol acyltransferase LDL, low-density lipoprotein LPL, lipoprotein lipase VLDL, very low-density lipoprotein. 

Rare genetic disorders, including Tangier disease and LCAT (lecithin cholesterol acyltransferase) deficiency, are associated with extremely low levels of HDL. Familial hypoalphalipoproteinemia is a more common disorder with levels of HDL cholesterol usually below 35 mg/dL in men and 45 mg/dL in women. These patients tend to have premature atherosclerosis, and the low HDL may be the only identified risk factor. Management should include special attention to avoidance or treatment of other risk factors. Niacin increases HDL in many of these patients. Reductase inhibitors and fibric acid derivatives exert lesser effects. 

Wilson, T.A., Meservey, C.M., and Nicolosi, R.J. 1998. Soy lecithin reduces plasma lipoprotein cholesterol and early atherogenesis in hypercholesterolemic monkeys and hamsters Beyond linoleate. Atherosclerosis 140, 147-153. 

Subbaiah, P. V., Chen, C. H., Albers, J. J., and Bagdade, J. D., Studies on the cofactor requirement for the acylation and hydrolysis reactions catalyzed by purified lecithin icholesterol acyltransferase Effect of low density lipoproteins and apolipoprotein A-I. Atherosclerosis 45, 181-190 (1982). 

Wl. Wallentin, L., Lecithin cholesterol acyl transfer rate in plasma and its relation to lipid and lipoprotein concentrations in primary hyperlipidemia. Atherosclerosis 26, 233-248 (1977). 

Lecithin plays an important role in the transport of fats and cholesterol from the liver to sites where they can be either used or stored. Since fats do not dissolve in water solutions like blood plasma, they are transported in spherical particles called lipoproteins. These particles can mix with water solutions because the water-friendly proteins, cholesterol and phospholipids are on the outside surface. The nonpolar fats associated with them make up the core, which is unexposed to water. Because lecithin is required for lipoprotein synthesis, a lecithin deficiency results in fats accumulating in the liver and leads to liver damage. Lecithin deficiency also leads to increased amounts of cholesterol in the blood and atherosclerosis, a disease in which narrowing of the arteries is caused primarily by the deposit of fats from the bloodstream. 

Foger, B., Chase, M., Amar, M.J., Vaisman, B.L., Shamburek, R.D., Paigen, B., Fruchart-Najib, J., Paiz, J.A., Koch, C.A., Hoyt, R.F., Brewer, H.B., Jr., and Santamarina-Fojo, S. (1999) Cholesteryl Ester Transfer Protein Corrects Dysfunctional High Density Lipoproteins and Reduces Aortic Atherosclerosis in Lecithin Cholesterol Acyltransferase Transgenic Mice, J. Biol. Chem. 274, 36912-36920. 

More than 80% of the cholesteryl esters (CE) found in human plasma derive from the reaction of lecithin cholesterol acyl transferase (LCAT). Since the content of CE in plasma high positively correlates with the incidence of atherosclerosis and myocardial infarction, there has been in the past and still is great interest in investigation of the enzymes involved in lipoprotein metabolism. This overview summarizes some general features, with particular emphasis on investigations carried out in our laboratory (a) the substrates of LCAT in plasma (b), the influence of LCAT on the Upoprotein spectrum (c) the distribution of formed CE after the action of LCAT (d) the impact of cholesteryl ester transfer/exchange protein (CETP) on Upoprotein metabolism. 

Lipid removal may be a critical factor in plaque formation and the location of lecithin-cholesterol trans-acylase in the arterial wall could play an important role since cholesterol is rapidly exchanged" with the blood while cholesterol ester is not. Kuo in an editorial cites the evidence for the theory that a dlsturbemce in carbohydrate metabolism can be responsible for atherosclerosis and should be included as one of the primary risk factors in coronary heart disease. In this regard, Clements and coworkers have shown the presence in aorta of aldose reductase, an enzyme which they feel provides a mechanism for the alteration of arterial metabolism by hyperglycemia. Another approach to molecular interactions was described by Levy and Day who concluded from their results that the low density lipoproteins are uniquely polycationic at the surface and that these ions react with the internal arterial macromolecular polyanions. 

Furbee JW Jr, Sawyer JK, Parks JS. Lecithin.cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice. J Biol Chem 2002 277 3511-3519. 

Ng DS, Maguire GF, Wylie J, et al. Oxidative stress is markedly elevated in lecithin cholesterol acyltransferase-deficient mice and is paradoxically reversed in the apolipoprotein E knockout background in association with a reduction in atherosclerosis. 7 Bio/ Chem 2002 277 11,715-11,720. 

The interest in lecithin as a protective factor against heart disease arose from the finding that high ratios of cholesterol to to phospholipids in the blood were correlated with the severity of atherosclerosis." Furthermore, it is established that the phospholipids of the platelet plasma membrane play an important role in blood coagulation."... 

Ntanios, FY, Jones, PJ and Frohlich, JJ (1998a) Dietary sitostanol reduces plaque formation but not lecithin cholesterol acyl transferase activity in rabbits. Atherosclerosis, 138, 101-110. 

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