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)

The effect of Olbetam on serum lipid and lipoproteins was studied in 30 diabetic patients with hyperlipidemia in four weeks trial. The dose of Olbetram was 500 mg/d. The results showed serum concentrations of TC, TG, and VLDL-C were decreased while HDL-C especially HDL2-C increased significantly after treatment. There were no significant changes in FBG, blood creatinine and urine acid. This result suggests Olbetam can improve dyslipidemia in NIDDM and was well tolerated by all patients.
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PMID:[Effect of olbetam on hyperlipidemia in NIDDM]. 873 67

In experimental nephrosis, a decrease in plasma albumin resulting from proteinuria causes a decreased in the plasma oncotic pressure. The existence of an osmoreceptor, which responds to the low oncotic pressure and produces a factor(s) that signals the liver to increase the secretion of plasma proteins, is postulated. The hyperlipidemia characteristic of the nephrotic syndrome results primarily from increased hepatic secretion of apolipoproteins and lipoproteins representing the entire density spectrum from VLDL, IDL, and LDL to HDL. Not all plasma proteins and apolipoproteins are affected to the same extent. Increased mRNA levels due to increased transcription have been shown for albumin and apolipoprotein A-1 (apoA-1). The increased secretion of VLDL, the major vehicle for triglyceride transport from the liver, appears to be due mainly to posttranscriptional events possibly related to increased lipogenesis. Once proteinuria begins, the demand for amino acids for albumin and apolipoprotein synthesis by the liver is increased. To meet this demand, protein catabolism in the peripheral tissues is increased. One manifestation of this process is a decrease in lipoprotein lipase which reduces VLDL catabolism, contributing to the sustained elevation of plasma VLDL. The spectacular overproduction of apoA-1 in nephrosis in the rat is accompanied by a decreased fractional catabolic rate (FCR), contributing to the maintenance of high levels of HDL. Urinary loss of HDL and its renal catabolism does not account for the decreased FCR. The reason for the decreased FCR is not known. Work with nephrotic rats overexpressing transgenic human apoA-1 has shown that human A-1 forms smaller HDL3-sized particles, rather than the larger HDL2 of the rat. This may contribute to the failure of HDL levels to increase in the human nephrotic syndrome. High plasma VLDL and LDL with normal or low HDL probably account for the increased incidence of coronary artery disease in the nephrotic syndrome.
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PMID:Lipoprotein metabolism in experimental nephrosis. 893 62

Apolipoprotein E (apoE) in high density lipoprotein (HDL) fraction (HDL-fr) was determined by the immunofixation method and turbidimetric immunoassay (TIA) after precipitation with phosphotungstic acid/MgCl2 in normolipidemic control subjects and patients with type IV hyperlipemia and hyper HDL-cholesterolemia. Immunofixation assay revealed two major bands of apoE in whole serum: one in the alpha-area and the other in the pre beta-area. ApoE in alpha-area (alpha-apoE) was identical to alpha-apoE in HDL-fr separated by ultracentrifugation but not to alpha-apoE in HDL-fr separated by precipitation (pHDL-fr). alpha-ApoE in pHDL-fr lacked the slower area of the band. Agarose column chromatography and gradient gel electrophoresis indicated that alpha-apoE belongs to early fractionated HDL, and that the precipitatable alpha-ApoE belongs to the higher molecular size HDL alpha-ApoE (%) estimated by immunofixation showed a strong positive correlation with apoE (%) in pHDL-fr. ApoE (%) in pHDL-fr was higher in case of hyper HDL-cholesterolemia and lower in type IV hyperlipemia than in controls, and was inversely correlated with serum triglycerides (TG) and positively with HDL-cholesterol (especially HDL2-cholesterol) in these subjects. It is suggested that the variation of apoE in pHDL-fr depends on the level of HDL2. Also, it may be suggested that apoE in pHDL-fr and precipitatable alpha-apoE belong to low and high molecular HDL2, respectively, and that apoE content in these particles is correlated with HDL2.
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PMID:Determination of apolipoprotein E in high density lipoprotein fraction by immunofixation method and turbidimetric immunoassay after precipitation. 922 65

Hyperlipidemia is frequently observed in patients who undergo renal, cardiac, bone marrow, or liver transplantation, and its contribution to the long-term morbidity and survival of patients with organ transplants may be substantial. In the few studies that have focused on the pediatric age group, findings have been inconsistent. The lipoprotein profile of 10 children after liver transplantation was characterized and compared with those in normal population controls and 10 healthy siblings. Plasma triglyceride and cholesterol concentrations were determined, lipoprotein fractions (very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoproteins [HDL2 and HDL3]) were isolated, their chemical compositions were analyzed (protein, phospholipids, triglycerides, free cholesterol, and cholesteryl ester), and the percent relative weight composition of the particles was calculated. Plasma triglyceride and VLDL cholesterol levels were higher post-liver transplantation (P < .05): triglycerides (mean +/- SD), 115.1 +/- 58.7 mg% versus 76.6 +/- 20.9 mg% in siblings and 60.0 +/- 25.0 mg% in normal population controls; very-low-density lipoprotein cholesterol (VLDL-C), 23.0 +/- 11.7 mg% versus 15.3 +/- 4.7 mg% and 13.0 +/- 8.0 mg%, respectively. Plasma triglyceride levels did not correlate with the length of the period after liver transplantation. Levels of LDL-C and total HDL-C and the relative weight composition of VLDL, LDL, HDL2, and HDL3 particles did not differ between post-liver transplantation children and controls. Posttransplantation, levels of HDL3, the normally predominant HDL subfraction, were decreased relative to HDL2 levels (HDL3, 1.3; HDL2, 2.3). Because this observed relative increase in larger cholesteryl ester-rich HDL particles (HDL2) may result from inhibition of cholesteryl ester-triglyceride transfer processes, cholesteryl ester transfer protein activity was assayed. Cholesteryl ester transfer protein activity did not differ between patients and controls. Thus, the lipoprotein changes observed in children post-liver transplantation are mild hypertriglyceridemia and a significant increase in HDL2 relative to HDL3. Because HDL2 is regarded as protective against atherosclerosis, this may be of clinical relevance.
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PMID:Lipoprotein changes in children after liver transplantation: mild hypertriglyceridemia and a decrease in HDL3/HDL2 ratio. 942 34

Modification of dietary fat composition may influence hemostatic variables, which are associated with increased risk of coronary heart disease (CHD). To address this question, we performed a controlled feeding study on 26 healthy male nonsmoking subjects with diets of differing fat composition. For the first 3 weeks, the subjects were given a diet calculated to supply 30% energy as total fat: 8% as monounsaturated, 4% as polyunsaturated, and 16% energy as saturated fatty acids, respectively (saturated diet). This was followed immediately by two diets taken in random order, each of 3-week duration and separated by an 8-week washout period on the subject's usual diet. Both diets were calculated to supply 30% of energy as fat: 14% monounsaturated, 6% as polyunsaturated, and 8% energy as saturated fatty acids. They both provided 5 g (approximately 1.7% energy) more of polyunsaturated fatty acids than the saturated fat diet; in one diet as long-chain n-3 fatty acids (n-3 diet) and in the other as linoleic acid (n-6 diet). Fasting plasma lipids, lipoproteins, and hemostatic factors were measured on the final 3 days of each dietary period. In a subset of 9 subjects the postprandial responses to a test meal were studied on the penultimate day of each period, each meal having the fat composition of its parent diet. On the n-3 diet compared with the n-6 diet, plasma triglyceride, HDL3 cholesterol, apoprotein AII, and fibrinogen concentrations were lower and HDL2 cholesterol concentration was higher (P = .0001, P = .003, P = .0001, P = .004, and P = .001, respectively). On both the n-3 and n-6 diets compared with the saturated diet, fasting plasma total and LDL cholesterol, apoprotein B, beta-thromboglobulin concentrations, and platelet counts were lower (P < .0001, P < .0001, P < .001, P < .01, and P < .05 respectively) and plasma Lp(a) and von Willebrand factor concentrations were higher (P = .02 and P < .01, respectively). Fasting factor VII coagulant activity (VIIc) was increased and apoprotein AI concentration reduced following the n-3 diet (P = .004 and P = .01, respectively) compared with the saturated diet. Plasma fibrinogen concentration was significantly greater following the n-6 diet than on the saturated diet (P = .02). Postprandially, plasma triglyceridemia was greater on the n-6 diet and lowest on the n-3 diet (P < .001) with the saturated diet being intermediate. Plasma VIIc was increased at 4 hours following the standardized test meals on the n-3 and n-6 diets (both P < .05) but not on the saturated diet. An increased intake of long chain n-3 fatty acids decreases fasting plasma triglyceride and apoprotein AII concentrations and increases HDL2 cholesterol concentrations and results in less postprandial lipemia but leads to an increase in VIIc. An increased intake of linoleic acid may raise plasma fibrinogen concentration. Decreasing the intake of saturated fatty acids reduces plasma LDL cholesterol and apoprotein B without affecting HDL cholesterol concentration independent of the type of polyunsaturated fatty acids in the diet. When advice is given to reduce saturated fat intake, it is important to ensure an appropriate ratio of n-3/n-6 fatty acids in the diet.
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PMID:Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. 943 92

Elevated concentrations of plasma cholesterol and triglycerides are characteristic of familial combined hyperlipidemia (FCHL) which may also present with reduced high density lipoprotein (HDL) cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by converting unesterified cholesterol to cholesterol ester in the process of maturation of HDL in the presence of its activator, apolipoprotein (apo) A-I. We hypothesised that alterations in LCAT activity or plasma concentrations or gene sequence of apo A-I could influence HDL metabolism in these patients. We studied cholesterol concentrations of high density lipoprotein subfractions and LCAT activity in 25 FCHL subjects and 48 controls. Total HDL (p=0.018) and HDL2 (p=0.008) were significantly decreased in the FCHL group compared with controls. After analyses with adjusted data only HDL2 remained significantly decreased in the FCHL group (p=0.050). The LDLc/HDLc and A-I/HDLc ratios were significantly elevated in the FCHL group (p <0.0001), the latter suggesting the existence of compositional differences in the HDL particles of the FCHL individuals. LCAT activity assessed in the FCHL (19.94+/-3.95 nmol/ml per h) and control (20.13+/-6.86 nmol/ml per h) groups showed no statistically significant differences. A significant positive correlation of LCAT activity with total HDL (r=0.42), HDL3 cholesterol (r=0.46) and apolipoprotein A-I (r=0.47) was observed in affected subjects but not in controls. An association between a Ga(-75)-A variation in the promoter region of the apo A-I gene and elevated concentrations of apo A-I (p=0.009) and apo C-III (p=0.041) was observed. This association was strongly influenced by the status of the subject providing further evidence for a regulatory role of this genetic region in the expression of FCHL. Our data suggests that LCAT activity is normal in FCHL and, therefore, does not account for the abnormalities observed in these patients essentially with regard to the HDL2 subfraction.
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PMID:Evidence against alterations in Lecithin:cholesterol acyltransferase (LCAT) activity in familial combined hyperlipidemia. 969 Sep 23

This study compared the efficacy and safety of a once-a-night, time-release niacin formulation, Niaspan (Kos Pharmaceuticals, Miami Lakes, FL), with plain niacin and placebo for the treatment of primary hypercholesterolemia. The study was conducted in nine academic lipid research clinics in a randomized, double-blind design. Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo. A total of 223 hypercholesterolemic adult men and women participated. Compared with placebo at 8 weeks, Niaspan versus plain niacin at 1.5 g/d showed comparable efficacy, comparably lowering total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raising high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances). After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled. At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001). Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated. In conclusion, Niaspan 1.5 g hour of sleep (hs) has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niacin in hyperlipidemic subjects. Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia.
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PMID:Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. 975 Dec 39

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.
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PMID:Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia. 992 Jan 46

Hyperlipidemia in the nephrotic syndrome results from increased synthesis and decreased catabolism of lipoproteins. The contribution of each to establishing blood lipid levels is unknown. Increased triglyceride rich lipoprotein concentration, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) primarily results from decreased clearance. This defect is due in part to reduced lipoprotein lipase (LPL) on the vascular endothelium resulting either from decreased synthesis or inadequate binding of this enzyme to endothelial surfaces. In contrast, both low density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] concentrations are increased. Unlike the case of albumin or transferrin, or apoA-I in the rat, LDL apoB 100 synthesis is not related to that of albumin, suggesting a different mechanism of regulation or a response to a stimulus that is not the same as that augmenting the synthesis of nonlipoproteins. Evidence is presented for synthesis of LDL through a mechanism that bypasses the normal delipidation pathway that requires a VLDL precursor for LDL formation. HDL concentration is normal but maturation is impaired leading to a shift from the larger HDL2 to the smaller HDL3, a variant that is less effective as a transporter of the LPL cofactor apolipoprotein C II.
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PMID:New insights into lipid metabolism in the nephrotic syndrome. 1041 29

Postprandial hypertriglyceridemia represents an independent risk factor for coronary artery disease. In the postprandial state, elevated levels of triglyceride-rich lipoproteins (TRL) are minor acceptors of HDL-cholesteryl ester (CE) transferred by CETP in normolipidemic subjects: indeed, LDL particles represent the major CE acceptors. In order to evaluate further the potential atherogenicity of lipoprotein particles characteristic of the postprandial phase in normolipidemic subjects, we determined the quantitative and qualitative features of apoB- and apoAI-containing lipoproteins over an 8-h period following consumption of a mixed meal. During postprandial lipemia, we observed a significant decrease (-12%) in plasma AI concentration (138+/-4 and 156+/-4 mg/dl, at 3 h and baseline, respectively, P<0.005). Concomitantly, a progressive increase (+13%) was detected in HDL2 concentrations (138+/-7 mg/dl at 4 h vs. 122+/-12 mg/dl at baseline, P<0.005), as well as a significant reduction (-9%) in HDL3 levels (137+/-6 mg/dl at 3 h vs. 150+/-4 mg/dl at baseline; P<0.05). Additionally, plasma LDL was reduced by 5% (247+/-12 mg/dl at 3 h vs. 260+/-15 mg/dl at baseline; P<0.05) 3 h following meal intake. Moreover, a significant reduction (-10%) occurred in the CE/TG ratio in LDL at 2 h postprandially (8+/-2 at 2 h vs. 9+/-3 at baseline; P<0.005). These changes reflected an increment (17+/-3 mg/dl at 3 h vs. 15+/-4 mg/dl at baseline; P<0.05) in LDL triglyceride concentrations. Despite the high CE acceptor capacity of LDL particles, no measurable increase in their CE content was detected during the postprandial phase. We demonstrated that CE accepted by LDL particles from HDL are secondarily transferred to chylomicrons by CETP. As chylomicrons displayed a 260-fold lower CE/TG ratio than LDL (0.03:1 and 7.8:1 in chylomicrons and LDL, respectively), CE-rich LDL may act to donate CE to chylomicrons. In conclusion, our data indicate that the presence of elevated levels of chylomicrons induces LDL to act as a secondary donor of CE during the postprandial phase.
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PMID:Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects. 1052 23


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