Hyperlipoproteinemia

Lipoprotein formed by hydrolysis of triglycerides in VLDL elevated in type III hyperlipoproteinemia. 

Hyperlipoproteinemias Famiiiai iipoprotein iipase deficiency (type i) Hypertriacylglycerolemia due to deficiency of LPL, abnormal LPL, or apo C-ll deficiency causing inactive LPL. Slow clearance of chylomicrons and VLDL. Low levels of LDL and HDL. No increased risk of coronary disease. 

Familial type III hyperlipoproteinemia (broad beta disease, remnant removal disease, familial dysbetalipoproteinemia) Deficiency in remnant clearance by the liver is due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor. Increase in chylomicron and VLDL remnants of density < 1.019 (P-VLDL). Causes hypercholesterolemia, xanthomas, and atherosclerosis. 

Inherited defects in lipoprotein metabofism lead to the primary condition of either hypo- or hyperlipoproteinemia (Table 26-1). In addition, diseases such as diabetes mellitus, hypothyroidism, kidney disease (nephrotic syndrome), and atherosclerosis are associated with secondary abnormal hpoprotein patterns that are very similar to one or another of the primary inherited conditions. Virtually all of the primary conditions are due to a defect at a stage in hpoprotein formation, transport, or destruction (see Figures 25—, 26-5, and 26-6). Not all of the abnormafities are harmful. 

Hyperlipoproteinemia, Type /, is characterized by the enhanced content of chylo-microns in the blood plasma simultaneously, the percentage of a- and p-lipopro-teins may be lowered. The triglyceride... 

Hyperlipoproteinemia, Type III, is a rare hereditary disease (also called familial dysbetalipoproteinemia) manifested by the occurrence of an uncommon P-lipo-protein form. Cholesterol and triglyceride contents in the patients may occasion-ally be 2-5 times superior to the norm. 

Hyperlipoproteinemia, Type IV, is characterized by increased contents of pre-P-lipoproteins and triglycerides (2-5 fold) in the blood plasma. Its incidence rate is higher in aged patients. Hereditary forms of this disease (called also familial hyperprebetalipoproteinemia) have been described. 

Hyperlipoproteinemia, Type V. This pathology is manifested by increased con-tents of chylomicrons, pre-P-lipoproteins, triglycerides, and cholesterol in the patients blood plasma. 

Secondary hyperlipoproteinemias, which arise from a disordered lipid tissue metabolism or its impaired control, are observed in diabetes mellitus, thyroid gland hypofunction, alcoholism, etc. 

Tissue Lipidoses. Hyperlipoproteinemias may lead to tissue lipidoses. Lipidoses can also arise from hereditary defects of the enzymes involved in the synthesis and breakdown of lipids in the tissues. We now discuss certain instances of tissue lipidoses. 

Atherosclerosis results from hyperlipoproteinemia. All of the lipoproteins, ex-cepting chylomicrons, are capable of penetrating the... 

Zocor (Simvastatin) Hypercholesterolemia Hyperlipoproteinemia Hypertriglyceridemia 3.9 1.3 1989 - UK 1991 - US Once daily... 

Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

Schonfeld G. Metabolic modes of action of statins in the hyperlipoproteinemias. Atherosclerosis 1998 141 203-207. 

Mann, W.A., Meyer, N., Weber, W., Meyer, S., Greten, H., and Beisiegel, U. (1995) Apolipoprotein E isoforms and rare mutations parallel reduction in binding to cells and to heparin reflects severity of associated type III hyperlipoproteinemia./. Lipid Res. 36, 517. 

Nicotinic acid in large doses used to treat hyperlipoproteinemia causes a cutaneous flush. The vasodilator) effect is due to... 

One type of hyperlipoproteinemia is characterized by elevated plasma levels of chylomicra, normal plasma levels of 3-lipoproteins, and the inability of any known drug to reduce lipoprotein levels. This is which of the following types of hyperlipoproteinemia ... 

Dyslipidemia is defined as elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides a low high-density lipoprotein (HDL) cholesterol or a combination of these abnormalities. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. Abnormalities of plasma lipids can result in a predisposition to coronary, cerebrovascular, and peripheral vascular arterial disease. 

BARs are useful in treating primary hypercholesterolemia (familial hypercholesterolemia, familial combined hyperlipidemia, type Ila hyperlipoproteinemia). 

Treatment of type I hyperlipoproteinemia is directed toward reduction of chylomicrons derived from dietary fat with the subsequent reduction in plasma triglycerides. Total daily fat intake should be no more than 10 to 25 g/day, or approximately 15% of total calories. Secondary causes of hypertriglyceridemia should be excluded, and, if present, the underlying disorder should be treated appropriately. 

Type III hyperlipoproteinemia may be treated with fibrates or niacin. Although fibrates have been suggested as the drugs of choice, niacin is a reasonable alternative because of the lack of data supporting a cardiovascular mortality benefit from fibrates and because of their potentially serious adverse effects. Fish oil supplementation may be an alternative therapy. 

Type V hyperlipoproteinemia requires stringent restriction of dietary fat intake. Drug therapy with fibrates or niacin is indicated if the response to diet alone is inadequate. Medium-chain triglycerides, which are absorbed without chylomicron formation, may be used as a dietary supplement for caloric intake if needed for both types I and V. 

The standard diet used in our experiments is a semipurified, cholesterol-free preparation that is composed of 25% protein, 40% sucrose, 13% coconut oil, 1% corn oil, 15% cellulose, 5% mineral mix, and 1% vitamin mix. This diet has been shown to induce an endogenous hypercholesterolemia and lead to atherosclerosis in rabbits and monkeys (4, 5). The specific question addressed by our series of investigations is whether the type of dietary protein, when all other dietary components are constant, can influence the development of hyperlipoproteinemia and atherosclerosis. More specifically, we have examined the effects of the individual amino acids, lysine and arginine, and their ratios in the diet on plasma and hepatic lipids as well as the development of arterial plaques. 

H30. Hiraga, T., Okubo, M., Kobayashi, T., Nakanishi, K., Sugimoto, T., and Murase, T., Serum lipoprotein(a) levels differ in different phenotypes of primary hyperlipoproteinemia. Metab., Clin. Exp. 42, 1327-1330 (1993). 

K22. Koenig, W., Hehr, R., Ditschuneit, H. H., Kuhn, K., Ernst, E., Rosenthal, J., and Hombach, V., Lovastatin alters blood rheology in primary hyperlipoproteinemia Dependence on li-poprotein(a). J. Clin. Pharmacol. 32, 539-545 (1992). 

Sandholzer, C., Feussner, G., Brunzell, J., and Utermann, G., Distribution of apolipopro-tein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia. J. Clin. Invest. 90, 1958-1965 (1992). 

Carnitine Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH]... 

Chappell, D.A. (1989) High receptor binding affinity of lipoproteins in atypical dysbetahpo-proteinemia (type III hyperlipoproteinemia). J. Clin. Invest., 84, 1906-1915. 

Hyperlipoproteinemias can be caused genetically (primary h.) or can occur in obesity and metabolic disorders (secondary h). Elevated LDL-cho-lesterol serum concentrations are associated with an increased risk of atherosclerosis, especially when there is a concomitant decline in HDL concentration (increase in LDL HDL quotient). 

Treatment Various drugs are available that have different mechanisms of action and effects on LDL (cholesterol) and VLDL (triglycerides) (A). Their use is indicated in the therapy of primary hyperlipoproteinemias. In secondary hyperlipoproteinemias, the immediate goal should be to lower lipoprotein levels by dietary restriction, treatment of the primary disease, or both. 

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