Essential hyperlipoproteinemias, lipoproteins

Chylomicron remnants and very low density lipoprotein (VLDL) remnants are rapidly removed from the circulation by receptor-mediated endocytosis. ApoE, the major apolipoprotein of the chylomicron in the brain, binds to a specific receptor and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. Defects in apolipoprotein E result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants (Mahley et al., 1999). In the brain, lipidated apoE binds aggregated in a isoform-speciflc manner, apoE4 being much more effective than the other forms,... 

Cholesterol and triglycerides, as the major plasma hpids, are essential substrates for cell membrane formation and hormone synthesis and provide a source of free fatty acids. Hyperlipidemia is defined as an elevation of one or more of cholesterol, cholesterol esters, phospholipids, or triglycerides. Lipids, being water immiscible, are not present in free form in the plasma but rather circulate as hpoproteins. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. The density of plasma lipoproteins is determined by their relative content of protein and lipid. Density, composition, size, and electrophoretic mobility divide lipoproteins into four classes (Table 21-1). 

The major lipids found in the bloodstream are cholesterol, cholesterol esters, triglycerides, and phospholipids. An excess plasma concentration of one or more of these compounds is known as hyperlipidemia. Because all lipids require the presence of soluble lipoproteins to be transported in the blood, hyperlipidemia ultimately results in an increased concentration of these transport molecules, a condition known as hyperlipoproteinemia. Hyperlipoproteinemia has been strongly associated with atherosclerotic lesions and coronary heart disease (CHD) (1,2). Before discussing lipoproteins, their role in cardiovascular disease, and agents to decrease their concentrations, it is essential to examine the biochemistry of cholesterol, triglycerides, and phospholipids. 

Fredrickson and Lees (1965) have described as their type III hyperlipoproteinemia, individuals who, in addition to clinical and laboratory evidence of essential hypercholesterolemia, show elevation of VLDLP (pre-j8-lipoproteins) and are markedly susceptible to carbohydrate induction. In common with other endogenous hyperlipidemics, they manifest carbohydrate intolerance. 

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