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)

There are indications that treatment of hypercholesterolemia by means of drugs reduce risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinemia, and should be regarded as an adjunct to appropriate dietary therapy. Drug therapy should be strongly considered in patients with total cholesterol above 8-9 mmol/l on diet therapy only. Drug therapy should be considered at even lower concentrations of cholesterol when coronary heart disease is present and in familial forms of hyperlipidemia when increased risk of atherosclerosis has been documented. In patients with increased plasma concentrations of total cholesterol the drugs of choice are agents which enhance the rate of LDL catabolism (resins) or reduce the rate of LDL synthesis (nicotinic acid). Fibrates should be used when triglycerides and cholesterol are both increased. HMG CoA reductase inhibitors offer considerable promise in the therapy of patients with primary hypercholesterolemia. Probucol may be used in combination with other drugs, particularly when xanthomas are present in patients with familial hypercholesterolemia.
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PMID:[Drug therapy of hypercholesterolemia. Treatment of hypercholesterolemia in adults--a Norwegian therapeutic program 1988]. 270 70

Omega-3 fatty acids have been shown to lower plasma cholesterol and triglyceride concentrations in humans. However, the effects of these fatty acids on the interactions among lipid concentrations, platelet activity, and atherogenesis have not been characterized in humans or in animals with low density lipoprotein (LDL) receptor deficiencies. To test the hypothesis that omega-3 fatty acids exert a protective effect in LDL receptor-deficient animals by lowering hyperlipidemia, reducing platelet aggregation, and reducing the severity of atherosclerosis, we evaluated young homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits that were fed omega-3 fatty acids. One-month-old male and female WHHL rabbits were placed on either a control diet (standard laboratory rabbit chow) or a diet supplemented with Menhaden fish oil (MFO), which contained eicosapentaenoic acid (EPA). Consumption measurements during the 5 months of the study indicated that the MFO-fed group received 150 to 200 mg/kg/day of EPA. Six-month-old, MFO-fed, female WHHL rabbits had significantly lower plasma concentrations of total cholesterol (582 +/- 20 mg/dl vs. 856 +/- 44 mg/dl, control, p less than 0.05) and triglycerides (266 +/- 21 mg/dl vs. 459 +/- 15 mg/dl, control, p less than 0.05), with lower serum/plasma lipoprotein concentrations [very low density lipoprotein (VLDL), LDL, high density lipoprotein (HDL)] compared to control female WHHL rabbits. Male MFO-fed rabbits had only significantly lower VLDLs (46 +/- 9 mg/dl) compared to control male WHHL rabbits (156 +/- 9 mg/dl, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dietary omega-3 fatty acid on serum lipids, platelet function, and atherosclerosis in Watanabe heritable hyperlipidemic rabbits. 275 81

Cholesteryl ester transfer from solid-phase bound HDL to endogenous plasma HDL or VLDL/LDL was determined in 50 patients with primary disorders of lipid metabolism and 27 normolipidemic subjects. Transfer to the plasma HDL pool was significantly reduced in familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia and dysbetalipoproteinemia. Subfractionation of HDL revealed that the lipid transfer to HDL3 was significantly reduced in all patient groups while transfer to HDL2 was increased in those with dysbetalipoproteinemia and familial hypertriglyceridemia. Transfer to LDL and VLDL was increased only in patients with dysbetalipoproteinemia and hypoalphalipoproteinemia. Reduced transfer to HDL occurred in samples with altered HDL composition; particularly where HDL-triglyceride was significantly increased and HDL-cholesteryl esters were reduced. Transfer of cholesteryl ester to HDL3 was significantly decreased in patients with vascular disease. These findings indicate that impaired interaction of cholesteryl ester transfer protein with the HDL3 pool may contribute to the risk of coronary heart disease in patients with specific plasma lipid abnormalities.
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PMID:Relationship between cholesteryl ester transfer activity and high density lipoprotein composition in hyperlipidemic patients. 275 50

This study examines the potential influence of genetic variation on the metabolism of LDL. Restriction fragment length polymorphisms (RFLP) of the gene coding for apo B were identified using the endonucleases Xba I, Eco RI, and Msp I in a group of 19 subjects with moderate hyperlipidemia. There was a significant association between the Xba I polymorphism and the total fractional clearance rate (FCR) of LDL. The individuals with the X1X1 genotype had, on average, a 22% higher FCR (P less than 0.025) than those with the genotype X2X2 (X2 allele = presence of Xba I cutting site). This difference was attributable to increased clearance by the receptor-mediated pathway of LDL catabolism. In this group of subjects, there was no association of LDL kinetic parameters and RFLPs of the LDL receptor gene or the AI- CIII- AIV gene cluster. The data suggest that variation in apo B itself, presumably acting through variable binding to the LDL receptor, makes a significant contribution to the rate of catabolism of LDL.
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PMID:Catabolic rate of low density lipoprotein is influenced by variation in the apolipoprotein B gene. 290 32

Lymphocyte proliferation stimulated by mitogenic lectins is dependent on exogenously supplied cholesterol when endogenous cholesterol synthesis is blocked with the specific inhibitor mevinolin. Lymphocytes from patients homozygous for familial hypercholesterolemia (FH) lack low density lipoprotein (LDL) receptors, and, therefore, these patients cannot use LDL cholesterol to support proliferation when endogenous sterol synthesis is blocked. Thus, LDL receptors are required for the uptake of exogenous lipoprotein cholesterol by proliferating lymphocytes. As a result, the number of functional receptors can be assessed when endogenous sterol synthesis is inhibited and when limiting concentrations of LDL are employed to support lymphocyte proliferation. Lymphocytes from patients heterozygous for LDL receptor abnormalities can be distinguished from normal lymphocytes since the former require twice the concentration of LDL for proliferation. By contrast, in hyperlipidemia not caused by FH, lymphocyte LDL receptor activity is normal, indicating that plasma cholesterol levels do not account for abnormalities in LDL receptor function assayed in this way. Therapy with cholesterol-lowering drugs, however, can alter lymphocyte LDL receptor activity in patients with heterozygous FH. Patients with heterozygous FH respond to therapy with mevinolin and a bile-acid-binding resin by lowering plasma cholesterol levels. In some patients, treatment with cholesterol-lowering plasma cholesterol levels. In some patients, treatment with cholesterol-lowering plasma cholesterol agents is also associated with normalization of functional lymphocyte LDL receptor activity, thereby providing direct evidence that therapy can alter LDL receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of low density lipoprotein receptor abnormalities by assaying functional receptors on proliferating lymphocytes. 291 32

In the present report we describe a patient with multiple myeloma and long-standing paraproteinemia who developed xanthoma in the absence of an elevation in plasma cholesterol or triglyceride concentrations. Studies demonstrated that our patient's monoclonal IgG antibody interacted with apoprotein B-100. The LDL-antibody complex isolated from our patient did not affect the degradation of LDL by human fibroblasts, indicating that while IgG derived from our patient interacted with LDL it did not alter the metabolism of this lipoprotein by the LDL receptor pathway. Since the LDL receptor pathway is the major route of LDL metabolism, this probably explains why our patient was not hyperlipidemic. In contrast to an absence of effect on the LDL receptor, our patient's LDL-antibody complex stimulated cholesterol esterification within macrophages indicating the uptake and degradation of the LDL-antibody complex. The LDL-antibody complex inhibited the degradation of acetyl LDL by macrophages (scavenger pathway), demonstrating that our patient's LDL-antibody complex was recognized as a modified LDL. Moreover, mixing Ig from our patient with normal LDL also resulted in the normal LDL increasing the esterification of cholesterol by macrophages. One can hypothesize that our patient's monoclonal IgG-LDL complex interacted with the macrophage scavenger receptor, thereby resulting in the occurrence of xanthoma in the absence of hyperlipidemia.
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PMID:Cutaneous xanthoma in association with paraproteinemia in the absence of hyperlipidemia. 292 22

There is good epidemiologic evidence that hypertension is associated with a high risk of cardiovascular disease. However, primary intervention trials have failed to demonstrate that a reduction in blood pressure in hypertensive patients reduces morbidity and mortality from cardiac events. Since various antihypertensive drugs adversely affect lipoprotein metabolism, these drugs may increase associated coronary risk and offset the beneficial effects of lowering blood pressure. This article reviews the effects of various antihypertensive drugs on plasma lipids, lipoproteins, and apolipoproteins. They can be summarized as follows: thiazide-type diuretics cause a marked elevation of plasma triglycerides and very low-density lipoprotein (VLDL) and minor increases in total cholesterol and low-density lipoprotein (LDL), but have little effects on high-density lipoprotein (HDL). The nonselective beta-blockers do not significantly affect total cholesterol and LDL, but increase total triglycerides and VLDL and decrease HDL. The changes in plasma lipids and lipoproteins caused by cardioselective beta-blockers and beta-blockers with intrinsic sympathomimetic activity are qualitatively similar but less pronounced. Calcium antagonists and angiotensin-converting enzyme inhibitors appear to have no significant effects on plasma lipids. alpha 1-Inhibitors reduce total triglycerides, total cholesterol, VLDL, and LDL and increase HDL. The possible mechanisms by which antihypertensive drugs affect cellular lipid metabolism (e.g., LDL receptor, lipid synthesis, lipoprotein lipase, lecithin cholesteryl acyltransferase, acylcholesteryl acyltransferase, and cholesteryl ester hydrolase) are described. The clinical significance of changes in blood lipids and cellular lipid metabolism caused by antihypertensive drugs is not yet totally clear. Nevertheless, before antihypertensive drug treatment is initiated, blood lipid levels should be measured to identify preexisting hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of antihypertensives on plasma lipids and lipoprotein metabolism. 305 88

Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit HMG-CoA reductase. This new drug decreases cholesterol synthesis and apolipoprotein B concentrations, and increases LDL receptor activity without adverse effects on other products in the cholesterol pathway. In patients with heterozygous familial or polygenic (non-familial) hypercholesterolaemia, oral lovastatin 20 to 40 mg twice daily reduces plasma total cholesterol and LDL-cholesterol concentrations by 25 to 40% over a period of several weeks. Lovastatin also produces decreases in plasma triglyceride and VLDL-cholesterol concentrations, although to a lesser extent. In addition, small though significant increases in HDL-cholesterol concentrations have been observed. Combined administration of lovastatin with other lipid-lowering drugs results in further reductions in plasma total and LDL-cholesterol concentrations beyond those seen with either drug alone. From findings in short term studies, lovastatin appears to be well tolerated with a low incidence of side effects. However, liver function tests and eye examinations for possible lens opacities are advised, and further long term studies in larger groups of patients are necessary before the side effect profile of lovastatin will be clearly established. As would be expected at this relatively early stage of its clinical 'life,' lovastatin has not yet been studied in a manner that would determine its effect on cardiovascular mortality during long term administration. Nevertheless, if the substantial improvements to patients' lipid and lipoprotein profiles observed in short term studies are maintained during long term administration, then lovastatin will have an important role in the pharmacological management of hyperlipidaemia.
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PMID:Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia. 306 36

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) caused a dose-dependent decrease of adipose tissue lipoprotein lipase (LPL) activity and caused a concomitant increase in serum triglyceride concentration in the rabbit 10 d after single ip administration of either 1 or 50 micrograms/kg. Hepatic low-density lipoprotein (LDL) binding was markedly depressed and serum cholesterol concentrations were modestly increased relative to pair-fed control animals. Serum glucose concentrations were significantly lower in the rabbit administered TCDD compared to ad libitum or pair-fed control animals, although little change was observed in serum insulin concentration. Electron microscopic examination of aortic arches 20 d after a single ip administration of 50 micrograms TCDD/kg revealed ruffling, denudation, and sloughing off of the cell surface and the appearance of macrophage-like structures in the intima and media of the endothelial cells. These alterations resemble preatherosclerotic lesions typical in animals with hyperlipidemia. It is proposed that TCDD causes hyperlipidemia in the rabbit through suppression of LPL activity and LDL receptor binding.
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PMID:Rabbit serum hypertriglyceridemia after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 319 60

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia (P less than 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not (P less than 0.01), and in patients with corneal arcus (P less than 0.0001), ischaemic disease (P less than 0.01), tendon xanthomas (P less than 0.05) or xanthelasma (P less than 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp (r = 0.78; P = 0.013) and IgG Lp (r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.
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PMID:Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis. 324 Mar 31


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