Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two sensitive and accurate methods for the determination of apo B using polyclonal antibody for human purified LDL are reported. Modified one step EIA by sandwich method is highly sensitive and serum has to be diluted by 1,000-3,000 times, but suited for the diagnosis of hypo or abetalipoproteinemia, detailed analyses of lipoprotein subfractions and in vitro study of lipoprotein metabolism. Latex method is moderately sensitive (serum dilution: 100 times), automated, simple and accurate with CV, 1.5-2.5%. Serum apo B assay is useful not only for the diagnosis of hyperlipidemia, hypolipidemia, but also for the analyses of atherogenic lipoproteins which are frequently associated with large vessel atherosclerotic changes in diabetes, obesity and coronary, cerebral or peripheral vascular diseases. A family pedigree of elevated apo B with frequent association of diabetes (type 2 b) and prominent hypercholesterolemia with autoimmune apo B antibody has been described. In obesity, either hyperinsulinemia or hyperglycemia plays a role in the elevation of VLDL and IDL probably through hepatic overproduction of VLDL. The size of VLDL tends to be larger in VLDL while IDL and LDL seem to become smaller judging from relative lipid contents to apo B.
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PMID:[Highly sensitive apo B assay and its clinical significance]. 223 45

Prevention of vascular disease and acute pancreatitis is the goal of hyperlipidemia treatment. The risk of coronary heart disease (CHD) increases with increasing plasma cholesterol levels because low-density lipoprotein (LDL), the major carrier of cholesterol in the plasma, is atherogenic. High-density lipoprotein (HDL), especially the HDL2 subfraction, protects against CHD. Hypertriglyceridemia, although not an independent risk factor for CHD, is generally accompanied by low HDL cholesterol (HDLch), which may predispose to CHD. Reducing plasma LDL and raising HDL levels are thus goals in preventing CHD. Serum LDL levels may be lowered by reducing saturated fat and cholesterol intake; weight loss may decrease LDL but is more effective in lowering plasma triglycerides and raising HDLch. The percent of total calories from polyunsaturated, monounsaturated, and saturated fats should be less than 10%, up to 10-15%, and less than 10%, respectively. High cholesterol intake increases the flux of cholesterol, which may be harmful to arterial walls, but beyond a certain point does not increase plasma cholesterol levels. Some diets change the composition rather than the level of LDL and apoproteins. Weight reduction and maintenance are the most effective dietary measures to lower plasma triglycerides; omega-3 fatty acids (fish oils) have shown promise in reducing triglyceride but not cholesterol levels. Substitution of starch for sugar lowered triglyceride levels toward normal in hypertriglyceridemia patients. Fasting triglyceride levels rise in all individuals fed high-carbohydrate diets, but the high levels persist in hypertriglyceridemia patients. Weight loss, cessation of cigarette smoking, increased physical activity, good control of diabetes, and moderate alcohol use all raise HDLch levels. Vitamin E deficiency causes neurological sequelae in children with severe malabsorption problems due to abetalipoproteinemia or cholestatic liver disease.
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PMID:Nutritional management of plasma lipid disorders. 255 90

The search for plasma lipoproteins began at the turn of the century. It was not until 1949 that a meeting of the Faraday Society celebrated the separation of the alpha and beta lipoproteins. At that moment, ultracentrifugists in Berkeley were already busily converting "alpha" to high density lipoprotein and "beta" to low density lipoprotein; the modern era of lipoproteins had begun. Over the succeeding 10 years, a quarrel over whether the level of Sf 0-20 or cholesterol was the more powerful risk factor ended with an eclipse of the analytical ultracentrifuge and a surge of interest in the biological side of lipoproteins. The postheparin clearing factor became lipoprotein lipase, and free fatty acids were discovered. In 1960, abetalipoproteinemia and Tangier disease suggested that the apolipoproteins must be specific and spurred a hunt for their number and nature. The first amino acid sequences aroused speculation of "amphipathic helices." By 1970, conversion of hyperlipidemia to five types of hyperlipoproteinemia led to worldwide fascination with electrophoretic patterns, "floating beta," and "the Friedewald formula" as codes for genetic abnormalities leading to early coronary artery disease. A few years later, the appearance of "familial combined hyperlipidemia" confounded the phenotyping, and the discovery of the low density lipoprotein receptor heralded the coming of true genotypes. This is a Bethesda-based story of the "climb to base camp" preceding the joining of molecular biology with the research on lipoproteins, dyslipoproteinemia, and atherosclerosis.
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PMID:Phenotyping. On reaching base camp (1950-1975). 846 75

Dyslipidemia is said to be present when lipid or lipoprotein levels lie within a range which is known from epidemiological studies to be associated with secondary complications, in particular atherosclerosis of the coronary arteries, or when a lipid or lipoprotein grossly deviates from the norm as in abetalipoproteinemia, hypobetalipoproteinemia or the HDL deficiency syndromes. In most cases, dyslipidemia is due not to a single genetic or environmental factor, but to a combination of the effects of several genes of small effect (polygenes) and environment. In other cases, however, dyslipidemia is caused by a mutation in a single gene of large effect. In such cases, the extent and nature of the phenotype depends primarily on the identity of the gene involved, but is also modulated to an important degree by the nature of the mutation and the genetic and environmental background against which this mutation occurs. In addition, many cases of hyperlipidemia are secondary to other disorders such as hypothyroidism or renal dysfunction. Such disorders may also unmask or exacerbate a genetic lipoprotein disorder. Examples of the latter are the unmasking of type III hyperlipidemia by diabetes mellitus or the exacerbation of familial hypercholesterolemia by hypothyroidism.
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PMID:Lipoproteins and cardiovascular risk-from genetics to CHD prevention. 963 14

Microsomal triglyceride transfer protein (MTP) plays a central role on secretion of lipoprotein from the liver and the intestine. MTP catalyzes the transfer of triglyceride, cholesteryl ester and phosphatidylcholine between membranes and lipoproteins. In human, defect of MTP activity, result from mutations encoding the MTP large subunit, is the primary cause of abetalipoproteinemia. To investigate the association between hyperlipidemia with obese and MTP, We used Otsuka Long-Evans Tokushima Fatty rat, an animal model of obesity with visceral fat accumulation, hyperlipidemia. In animals, very-low density lipoprotein-triglyceride levels were elevated compared with the control rats. Hepatic mRNA levels of acyl-coenzyme A synthetase, and MTP were also elevated. These results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation may be involved in the pathogenesis of hyperlipidemia in obese animal models.
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PMID:[The role of microsomal triglyceride transfer protein in metabolism of apo B-containing lipoprotein]. 1063 97

Various epidemiological studies and lipid intervention trials have revealed that serum LDL-cholesterol level correlates to the incidence in ischemic heart disease, and decreasing the level can prevent cardiac events. Inherited diseases causing abnormal LDL-cholesterol levels are discussed in this article, including their animal models. Familial hypercholesterolemia, familial ligand-defective apolipoprotein B100, familial combined hyperlipidemia and cholesterol ester storage disease result in elevation of serum LDL-cholesterol. On the other hand, serum LDL-cholesterol is decreased in abetalipoproteinemia and familial hypobetalipoproteinemia. The development of genetic engineering technology has elucidated the mechanism of these genetic disorders and elaborated their animal models. Although most of them cause atherosclerotic or psychoneurological diseases, fundamental therapy remains to be established, such as gene therapy.
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PMID:[Genetic disorders causing abnormal LDL-cholesterol levels]. 1063 3

Current approaches to the treatment of lipid disorders are inadequate for a substantial number of patients with severe hyperlipoproteinemia, isolated low high-density lipoprotein (HDL) cholesterol levels, or other molecular disorders of lipoprotein metabolism. Therefore, dyslipidemias remain important targets for the development of novel therapies. Gene therapy is a logical therapeutic approach to monogenic lipoprotein disorders, such as homozygous familial hypercholesterolemia, familial lipoprotein lipase deficiency, familial lecithin-cholesterol acyltransferase deficiency, and abetalipoproteinemia, for which current therapies are inadequate. Gene therapy could also be used to increase expression of certain proteins, such as apolipoprotein A-I as a strategy to raise HDL cholesterol levels or apoE as a strategy for severe combined hyperlipidemia. With further progress in the development of vectors, gene therapy for severe dyslipidemia is likely to become a clinical reality.
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PMID:Gene therapy for dyslipidemia: clinical prospects. 1112 93

Fatty liver disease is now recognized as a major health burden, due to the greater number of cases that are being diagnosed. This trend could partly be explained by the increased use of liver ultrasonography in asymptomatic patients for various reasons, mainly persistent transaminase elevation. The most commonly reported risk factors associated with fatty liver disease are chronic alcohol intake, obesity, type 2 diabetes mellitus, hyperlipidemia, and some drugs. When these factors have been ruled out in a patient with a fatty liver, less frequent causes such as certain inherited metabolic disorders should be considered. Familial hypobetalipoproteinemia is characterized by an alteration of apolipoprotein B (apo B) synthesis, leading to the secretion of truncated forms of the protein, which in turn leads to a marked reduction in excretion of very low-density lipoproteins from the liver and consequently to lipid deposits, especially triglycerides, in the hepatocytes. We report the case of a 23-year-old man who met the diagnostic criteria for heterozygous familial hypobetalipoproteinemia. He presented with mild transaminase elevation and fatty liver. Total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and apo B were below normal limits, while levels of high-density lipoprotein cholesterol were normal. Lipid profile determination and liver ultrasonography of first and second-degree relatives were also performed. Molecular studies of the index case revealed an unaffected apo B gene.
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PMID:[Hepatic steatosis associated with heterozygotic familial hypobetalipoproteinemia]. 1505 12

Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. These agents may potentially play a role, alone or in combination, in the treatment of hypercholesterolemia or hypertriglyceridaemia. Clinical applications of MTP inhibitors initially focused primarily on high-dose monotherapy in order to produce substantial reductions in LDL-cholesterol levels but these proved to induce significant hepatic steatosis and transaminase elevations. However, likely orphan indications for MTP inhibitors, where a different risk-benefit profile applies, include patients with homozygous familial hypercholesterolemia where statins often show a low response. Development of MTP inhibitors has continued to enter clinical trials at lower doses or in formulations aimed at utilizing their efficacy while avoiding their side effects. These have shown promising results in reducing cholesterol, triglycerides and apolipoprotein B with a far lower incidence of, often, transient side-effects. The clinical efficacy and safety of MTP inhibition in patients with hyperlipidaemia remains to be fully determined and to be proven in both surrogate and clinical endpoint trials but there may be a role for these agents in orphan indications for rarer severe hyperlipidaemias.
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PMID:New lipid modulating drugs: the role of microsomal transport protein inhibitors. 2141 29