Lipoproteins cholesterol content

The use of plant sterols—(3-sitostcrol and sitostanol in consumer products to decrease cholesterol is supported by numerous clinical studies that document their efficacy in lowering mild hyperlipidemia (Jones et al., 1998 Hallikainen and Uusitupa, 1999). Although the normal diet contains plant sterols that range from 160 to 360 mg/day, a 5- to 10-fold increase is required to exert a cholesterol-lowering effect. Consumer products with increased amounts of phytosterols that exceed the content found in the diet have been made available to the consumer. In evaluating the efficacy of including sitostanol ester in margarine as a dietary supplement for children with familial hypercholesterolemia (FH), it was found that serum total cholesterol (TC), intermediate density lipoprotein-cholesterol and LDL-cholesterol levels fell while the HDL-cholesterol/LDL-cholesterol ratio was elevated. 

Kirby, C., Clarke, J., and Gregoriadis, G. (1980), Cholesterol content of small unilamellar liposomes controls phospholipid loss to high density lipoproteins in the presence of serum, FEBS Lett., Ill, 324-328. 

The quantitative relationship between cholesterol intake and cholesterol levels is still controversial, especially because in humans, there appears to be a high individual variability in processing of dietary cholesterol. However, numerous animal and human studies support the concept that dietary cholesterol can raise LDL-cholesterol levels and change the size and composition of these particles as well. LDL particles become larger in size and enriched in cholesterol esters. Mechanisms contributing to these events include an increase in hepatic synthesis of apoB-containing lipoproteins, increased conversion of VLDL remnants to LDL, or a decrease in the fractional catabolic rate for LDL. Reduced LDL receptor activity due to an increase in hepatic cholesterol content, secondary to excess dietary cholesterol, may lead to a decreased uptake of both LDL and VLDL remnants. 

The typical sunflower oil composition is 66-72% linoleic acid, 12% saturated acids (palmitic and stearic), 16-20% oleic acid, and less than 1% a-linolenic acid. An increase in low-density lipoprotein cholesterol (LDL-C) and a decrease of high-density lipoprotein cholesterol (HDL-C) are believed risk factors of coronary heart disease (CHD). Diets rich in saturated fat increase plasma total and LDL-C. Traditional high-linoleic sunflower oil has always been regarded as healthy because of its high content of polyunsaturated fatty acids (PUFA) and relatively low content in saturated fatty acids. 

The consumption of foods high in TFA has been shown to raise low-density lipoprotein cholesterol (LDL or bad cholesterol), which increases the risk of developing coronary heart disease (CHD). This prompted the Food and Drug Administration (FDA) to require mandatory labeling of the fran -fat content in foods. Food manufacturers have to comply by January 1, 2006. The FDA s chemical definition of TFA or trans-fats (TF) is unsaturated fatty acids that contain one or more isolated (i.e., nonconjugated) double bonds in the frani-configuration. ... 

Lipid transport mechanisms exist that shuttle cholesterol and triglycerides among the liver, intestine, and other tissues. Normally, plasma lipids, including lipoprotein cholesterol, are cycled into and out of plasma and do not cause extensive accumulation of dcpo.sits in the walls of arteries. Genetic factors and changes in hormone levels affect lipid transport by altering enzyme concentrations and apoprotein content, as well us the number and activity of lipoprotein receptors. This complex relationship makes the treatment of all hyperlipoproteinemias by a singular approach difficult, if not impractical. 

Figure 26-21 Reverse cholesterol transport pathway. HDl High-density lipoproteins LDL, low-density lipoproteins tDL, intermediate-density lipoproteins HTL, hepatic lipoprotein lipase LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein apo E, apoiipoprotein E. Cholesterol is removed from macrophages and other arterial wall cells by an HDL-mediated process. The LCAT esterifies the cholesterol content of HDL to prevent it from reentering the ceils. Cholesterol esters are delivered to the liver by one of three pathways ( ) cholesterol esters are transferred from HDL to LDL by CETP and enter the liver through the specific LDL receptor pathway (2) cholesterol esters are selectively taken from HDL by HDL receptors and HDL particles are returned to circulation for further transport or (3) HDL have accumulated apo E and therefore the particles can enter the liver through remnant receptors, (From Gwynne JT. High density lipoprotein cholesterol levels as a marker of reverse cho/estero/ tronsport./ m j Cardiol I989 64 10G-I7G. Copyright 1989, with permission from Excerpta Medico Inc.)...

Plasma lipoproteins, as macromolecular complexes that vaiy considerably in size, composition, and function, present considerable analytical challenge (see Table 26-4). For clinical purposes, lipoprotein concentrations have been traditionally expressed in terms of their cholesterol content, because they carry virtually all of the cholesterol that circulates in the plasma. This simplifies the methods used to measure lipoproteins because the fipoprotein fractions of interest have only to be separated from each other the other plasma proteins do not have to be removed. 

Various technologies have been used to measure plasma lipids and lipoproteins and lipoprotein subfractions, including enzymatic, immunochemical, and chemical precipitation reagents, and physical methods, such as ultracentrifugation, electrophoresis, column chromatography, and others. Such methods have been reviewed extensively. As mentioned earlier, however, the cholesterol content of any particular lipoprotein class can vaiy somewhat from individual to individual. Moreover, although different methods of lipoprotein separation may produce similar lipoprotein fractions, they usually do not produce identical fractions, giving rise to systematic biases between methods that purport to measure the same component. The present discussion focuses primarily on methods and procedures commonly used in clinical practice for lipid and lipoprotein measurements. 

Intermediate-Density (Remnant) Lipoproteins Remnant lipoproteins include the lipolytic products of catabolism of the triglyceride-rich lipoproteins, VLDL and chylomicrons, occurring in the VLDL and LDL ranges. A traditionally defined fraction at the lighter end of the LDL density range, the IDL portion comprises the 1.006 to 1.019 g/mL fraction, which is obtained by sequential ultracentrifugation for quantitation, generally in terms of cholesterol content. 

Since LDL is the principal plasma-cholesterol carrier and its concentration in plasma correlates positively with the incidence of coronary heart disease, LDL is the most intensively studied plasma lipoprotein. Production in humans, via the pathway VLDL IDL LDL, accounts for all of the LDL normally present. However, in familial hypercholesterolemia or on a high-cholesterol diet, VLDL is produced that is higher in cholesterol content, smaller in size, and within the LDL density range (1.019-1.063 g/mL). 

For HDL-C measurements, similar developments have taken place with direct homogeneous assays, which eliminate the need for precipitation and separation steps (Okazaki et al. 1997 Reed 1997 Warnick, Nauck, and Rifai 2001). The differing proportions of lipoproteins (and their cholesterol content) in the plasmas of the various laboratory species mean that the suitability of these homogeneous and precipitation methods must be checked if meaningful results are to be obtained, particularly when lipoprotein antibodies are used (Warnick and Albers 1978 Hoffmann et al. 1985 Sjoblom and Eklund 1989 Tschantz and Sunahara 1993 Escola-Gil et al. 1999 Ensign et al. 2006). 

There are two pieces of evidence in the literature that support the prediction that the cholesterol content of tissue membranes of children with SCD is increased relative to children without this hematological disease, and both are related to the phenomenon of reverse cholesterol transport, which allows the liver to eliminate excess cholesterol in peripheral tissues. Central to the reverse cholesterol transport is the efflux of cholesterol from the membranes followed by the lecithin-cholesterol acyltransferase-catalyzed acylation of that cholesterol with a fatty acid from phosphatidylcholine. This reaction is activated by high density lipoprotein (HDL) and is favored by n-3 PUFA in the HDL particles. The cholesterol esters are finally delivered to the liver bound to low density lipoprotein or by very low density Hpoproteins. 

From the foregoing it is natural that treatments designed to modify plasma lipoprotein concentrations have been sought with vigour. In particular, the aim of reducing serum cholesterol and LDL concentrations has been to induce a decrease in the cholesterol content and size of atheromatous lesions... 

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