Lipoprotein hyperlipoproteinemia

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

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 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. 

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

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-... 

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. 

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). 

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). 

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

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. 

Ciprofibrate 131 is a potent, long-acting hypolipidemic agent. It is effective in type Ila, Ilb, III and IV hyperlipoproteinemias and produces a beneficial elevation of the anti-atherogenic high density lipoprotein, Eq. (52) [182]. 

Fic. 3. Protein components of human serum very high-density lipoprotein (VLDL) apoprotein (Apo). According to the experience gained in this laboratory, this component is negligible. As shown by Brown et al. (B9, BIO), it becomes relevant in VLDL of patients with types IV and V hyperlipoproteinemia,... 

G3. Ganesan, D., Bradford, R. H., Ganesan, W., McConathy, W. J., Alaupovic, P., and Hazzard, W. R., Substrate specificity and polypeptide activation of postheparin plasma lipoprotein lipase in type III hyperlipoproteinemia (broad disease). CireukUion 46, Suppl. II, 248 (1972). 

It is considered the most effective drug for lowering levels of cholesterol, triglycerides, and very low-density lipoproteins in the plasma and for moderately increasing the number of high-density lipoproteins. It is used for treating hyperlipoproteinemia that cannot be corrected by a special diet or physical exertion. Synonyms of lovastatin are lovalip, meva-cor, mevinacor, and sivlor and those of mevastatin are CS-500 and ML-236 B. 

Dextrothyroxine speeds up the decomposition of cholesterol and lipoproteins, thus activating catabolism of cholesterol in the liver, which results in cholesterol being more intensively transformed into bile salts. It lowers the level of low-density lipoproteins in the plasma and very low-density lipoproteins in fatty tissue. It is recommended for treating hyperlipoproteinemia. Synonyms of this drug are choloxin, lizolipin, natexin, travenon, and others. 

Familial hyperlipoproteinemia Estrogen therapy may be associated with massive elevations of plasma triglycerides leading to pancreatitis and other complications in patients with familial defects of lipoprotein metabolism. 

Drug Reduced CHD Risk Lipoprotein Affected Hyperlipoproteinemia Treated In Singly Combination Principal Adverse Effects... 

The answer is a. (Hardman, pp 875-898.) In type I hyperlipoproteinemia, drugs that reduce levels of lipoproteins are not useful, but reduction of dietary sources of fat may help. Cholesterol levels are usually normal, but triglycerides are elevated. Maintenance of ideal body weight is recommended in all types of hyperlipidemia. Clofibrate effectively reduces the levels of VLDLs that are characteristic of types 111, IV, and V hyperlipoproteinemia administration of cholestyramine resin and lovastatin in conjunction with a low-cholesterol diet is regarded as effective therapy for type 11a, or primary, hyperbetalipoproteinemia, except in the homozygous familial form. 

Plasma lipids are transported in complexes called lipoproteins. Metabolic disorders that involve elevations in any lipoprotein species are termed hyperlipoproteinemias or hyperlipidemias. Hyperlipemia denotes increased levels of triglycerides. 

Hazzard WR, Porte D Jr., Bierman EL (1972) Abnormal lipid composition of very low density lipoproteins in diagnosis of broad-beta disease (type 3 hyperlipoproteinemia). Metabolism 21 1009-1019... 

Production of LDL from VLDL in the plasma With these modifications, the VLDL is converted in the plasma to LDL. An intermediate-sized particle, the intermediate-density lipoprotein (IDL) or VLDL remnant, is observed during this transition. IDLs can also be taken up by cells through receptor-mediated endocytosis that uses apo E as the ligand. [Note Apolipoprotein E is normally present in three isoforms, E2, E3, and E4. Apo E2 binds poorly to receptors, and patients who are homozygotic for apo E2 are deficient in the clearance of chylomicron remants and IDLs. The individuals have familial type III hyperlipoproteinemia (familial dysbetalipoproteinemia, or broad beta disease), with hypercholesterolemia and premature atherosclerosis. Not yet understood is the fact that the E4 isoform confers increased susceptibility to late-onset Alzheimer disease.]... 

Apo C-ll activates lipoprotein lipase, which degrades the chylomicron s triacylglycerol to fatty acids and glycerol. The fatty acids that are released are stored (in the adipose) or used for energy (by the muscle). The glycerol is metabolized by the liver. Patients with a deficiency of lipoprotein lipase or apo C-ll show a dramatic accumulation of chylomicrons in the plasma (type 1 hyperlipoproteinemia, familial lipoprotein lipase deficiency, or hypertriacylglycerolemia)... 

In normolipidemic subjects, apoE is found not only in HDLc-like particles but also in two other fractions associated with triglyceride-rich lipoproteins. These are VLDL, and a lipoprotein class intermediate in size between VLDL and LDL (G3). The latter may be the normal counterpart of the (3-VLDL which accumulates in Type III hyperlipoproteinemia and in cholesterol-fed animals. 

ApoE-containing VLDL in hyperlipidemic subjects has been shown to be both the product of particles less rich in apoE (as judged by the apoE apoC ratio) and the precursor of apoE-rich intermediate-density lipoprotein (N2). In cholesterol-fed dogs (F5) and humans with Type III hyperlipoproteinemia (F5, K3) there is evidence (based on the form of apoB, B-48, or B-100, and the response to fasting) that apoE-rich (3-VLDL contains remnants of both VLDL and chylomicrons. 

F5. Fainaru, M., Mahley, R. W., Hamilton, R. L., and Innerarity, T. L., Structural and metabolic heterogeneity of (J-very low density lipoproteins from cholesterol-fed dogs and from humans with Type III hyperlipoproteinemia. J. Lipid Res. 23, 702-714 (1982). 

M9. Mahley, R. W., Atherogenic hyperlipoproteinemia. The cellular and molecular biology of plasma lipoproteins altered by dietary fat and cholesterol. Med. Clin. North Am. 66, 375-402 (1982). 

P8. Patsch, W., Lisch, H. J., Sailer, S., and Braunsteiner, H., Initial cholesterol esterification rate in hyperlipoproteinemia Effects of triglyceride-rich lipoproteins. Eur. J. Clin. Invest. 8, 209-213 (1978). 

U5. Utermann, G., Jaescbke, M., and Menzel, J., Familial hyperlipoproteinemia type III Deficiency of a specific apolipoprotein (apo E-III) in the very-low-density lipoproteins. FEBS Lett. 56, 352-355 (1975). 

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