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)

Plasma triglycerides are increased in the majority of patients with advanced renal failure but cholesterol is not. HDL cholesterol is reduced while LDL IDL and VLDL cholesterol is increased. Lecithin:cholesterol acyltransferase (LCAT), an enzyme necessary for HDL maturation, is reduced in chronic renal failure (CRF). As a consequence, while all subtypes of HDL are reduced, the small HDL3 subtype is relatively enriched at the expense of the larger, more functional HDL2 subtype. Triglycerides are increased in all lipoprotein fractions. HDL-associated apolipoproteins, apo A-I and A-II are decreased, while apo B is increased. Lipoprotein catabolic rate is reduced, but the cause of hyperlipidemia is multifactorial; reduced lipoprotein lipase (LPL) activity, increased concentration of apo C-III (a specific inhibitor of LPL) in plasma, secondary hyperparathyroidism, insulin resistance. Hyperlipidemia is not corrected by dialysis. Lipid levels are somewhat higher in CAPD patients, possibly as a consequence of increased glucose absorption or as a consequence of transperitoneal HDL losses. Triglycerides decrease and cholesterol increases following transplantation. Oxidized lipids are increased in plasma of patients with CRF. Plasma polyunsaturated fatty acids are decreased and saturated fatty acids increased. The same changes occur in the lipid bilayers composing leukocytes and red blood cell membranes. These changes result in altered membrane fluidity, and are corrected by dialysis. While atherosclerotic disease is a leading cause of death in dialysis patients, it is not certain that the specific lipid disorders of CRF are responsible for this morbidity, nor is it recommended at this time that qualitative abnormalities be treated pharmacologically in the absence of increased lipid levels.
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PMID:Hyperlipidemia of chronic renal failure. 798 78

Two subpopulations of apolipoprotein A-I-containing lipoproteins, those containing only apoA-I (LpA-I) and those containing both apoA-I and apoA-II (LpA-I/A-II), were isolated by immunoaffinity chromatography of plasma from 44 subjects, comprising four groups (male or female, with or without hyperlipidemia). ApoA-I-defined particles (LpAs) were assessed for their content of cholesteryl ester transfer protein (CETP) and for their ability to act as substrates for CETP. Although plasma CETP concentration was similar in all groups, the plasma concentration of LpA-I-associated CETP was significantly higher in females than in males (1.56 +/- 0.11 versus 0.93 +/- 0.13 mg/l, P < 0.05). In females, the major fraction of CETP was found in LpA-I, whereas in normolipidemic males CETP was evenly distributed between LpA-I and LpA-I/A-II, and in hyperlipidemic males the majority of CETP was found in LpA-I/A-II. In all groups, the percentage of CETP in LpA-I was correlated with the concentration of apoA-I in LpA-I (r = 0.64, P < 0.001). Native gradient gel electrophoresis of isolated LpAs showed that CETP was broadly distributed within different sized particles. LpA-I and LpA-I/A-II showed similar efficiency of CETP-mediated cholesteryl ester exchange with LDL. In conclusion, even though LpA-I has a much higher apparent affinity for CETP than LpA-I/A-II, both LpAs can bind CETP and act as equivalent CETP substrates in vitro. Thus, in subjects with low levels of LpA-I (notably hyperlipidemic males), most of the plasma neutral lipid exchange will involve LpA-I/A-II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gender effects on the distribution of the cholesteryl ester transfer protein in apolipoprotein A-I-defined lipoprotein subpopulations. 807 2

To gain insight into metabolic determinants of high density lipoproteins (HDL) containing apolipoproteins A-I and A-II (LpA-I/A-II) and those containing A-I, but devoid of A-II (LpA-I), the plasma concentration of LpA-I and LpA-I/A-II within the HDL2 and HDL3 density spectrum was measured in 14 normolipidemic male subjects on a standardized diet. Apolipoprotein plasma concentrations of HDL subspecies were compared with the magnitude of postprandial lipemia, activities of lipoprotein lipase and hepatic lipase in postheparin plasma, plasma lecithin:cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) mass. Plasma levels of LpA-I/A-II were 2.5 times higher than levels of LpA-I (123 +/- 20 vs. 48.3 +/- 22.1 mg protein/dl) and the partition of LpA-I and LpA-I/A-II between HDL2 and HDL3 differed in that the proportion of LpA-I associated with HDL2 was greater than that of LpA-I/A-II (23 +/- 19 vs. 6 +/- 6%, P < 0.002). With increasing levels of HDL2, the proportion of LpA-I in HDL2 increased (P < 0.002). Furthermore, levels of LpA-I and LpA-I/A-II were strongly correlated within the HDL2 but not within the HDL3 density region. Plasma levels of LpA-I, but not LpA-I/A-II, were inversely correlated with the magnitude of postprandial lipemia. However, activities of lipoprotein lipase and hepatic lipase tended to show stronger associations with the partition of LpA-I/A-II between HDL2 and HDL3 than with that of LpA-I. Within the HDL3, but not the HDL2 density spectrum, LpA-I/A-II exhibited a positive association with plasma LCAT activity, while LpA-I displayed an inverse association with plasma CETP mass. These results are consistent with differences in substrate properties of LpA-I and LpA-I/A-II for lipoprotein modifying enzymes and imply different, but overlapping metabolic pathways of LpA-I and LpA-I/A-II.
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PMID:High density lipoproteins with differing apolipoproteins: relationships to postprandial lipemia, cholesteryl ester transfer protein, and activities of lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase. 816 33

Hypoalphalipoproteinemia (HA) is a common finding in patients with premature coronary artery disease. To characterize the common familial forms of HA, we studied 102 families of probands with premature coronary artery disease; 40 probands (39.2%) had HA. Of these, 25 had at least one first-degree relative affected with HA; 11 had familial hypertriglyceridemia with HA (FTgHA); 10 had familial combined hyperlipidemia (FCH); and 4 had familial HA (FHA) with no other lipoprotein abnormalities. In the remaining 15 families, no lipoprotein abnormalities were observed in first-degree relatives. We measured apolipoprotein (apo) A-I, B, C-III, and E levels as well as lipoprotein particle (Lp) levels of LpA-I (containing apoA-I only), LpA-I:A-II (containing both apoA-I and A-II), LpB:E, and LpB:C-III. Compared with a reference group of healthy men (n = 103) and women (n = 106), probands with familial forms of HA had lower high-density lipoprotein cholesterol levels by selection criteria. Triglyceride levels were higher in FTgHA and FCH probands than in the reference group or FHA subjects. Despite selection of FTgHA and FCH by low-density lipoprotein (LDL) cholesterol, the latter was not significantly different between the three groups and the reference group. ApoA-I levels were decreased in FCH, FHA, and FTgHA probands, and LpA-I and LpA-I:A-II were lower in FHA and FTgHA probands. ApoB levels were significantly higher in all familial HA groups compared with the reference group, being highest in FCH individuals, but not significantly higher between FCH, FTgHA, or FHA probands. LpB:E levels were higher in the FCH and FTgHA groups than in the reference group. There were no significant differences between groups for apoE, apoC-III, and LpB:C-III. LDL particle size was smaller in all three forms of FHA, which, in combination with higher apoB levels, reflects an increased number of smaller, denser LDL particles. Affected children had, on average, higher apoB and LpB:E levels than nonaffected siblings. Our data suggest that common forms of FHA in subjects with coronary artery disease represent a spectrum of overlapping disorders characterized by an increase in apoB-containing lipoproteins, especially LpB:E particles, and smaller, denser LDL particles. When using appropriate age- and gender-adjusted cutpoints, approximately half the offspring (in young adulthood) appeared to be affected.
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PMID:Familial hypoalphalipoproteinemia in premature coronary artery disease. 824 Oct 92

The plasma concentration, particle size, and chemical composition of high density lipoproteins (HDLs) are associated with the metabolism of triglyceride-rich lipoproteins (TGRLs). During alimentary lipemia there is active exchange of lipids and apolipoproteins between HDL and apolipoprotein B-containing lipoproteins. Whereas HDL has been assigned a protective role against the development of atherosclerosis, alimentary lipemia has been proposed to represent a potentially atherogenic state. We examined plasma HDL concentration, particle size, and composition and their relations to postprandial TGRLs in 32 postinfarction patients and 10 healthy control subjects after intake of a standardized oral fat load of a mixed-meal type. All patients had undergone coronary angiographies in connection with the myocardial infarction and around 5 years thereafter. The plasma HDL cholesterol concentration decreased significantly in response to the oral fat load, particularly in hypertriglyceridemic patients, with a concomitant increase of HDL triglycerides. A limited and reversible yet consistent increase of HDL particle size (1-2%) was seen 6 hours after intake of the oral fat load on nondenaturing gradient gel electrophoresis (GGE) in both patients and control subjects. Virtually no changes in the plasma concentration of HDL GGE subclasses, lipoproteins containing apolipoprotein A-I but no apolipoprotein A-II (LpA-I), or lipoproteins containing both apolipoproteins A-I and A-II (LpA-I:A-II) were induced in the postprandial state despite massive increases of large very low density lipoprotein (VLDL) and large chylomicron remnant levels (determined as apolipoproteins B-100 and B-48 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Strong inverse correlations with fasting plasma HDL cholesterol and the larger HDL GGE subspecies were found for large postprandial VLDL and large chylomicron remnants, whereas the corresponding relations for small VLDL and small chylomicron remnants were weaker. The relations of both large and small VLDL and chylomicron remnants to HDL cholesterol were confined to subjects in the lower fasting plasma HDL cholesterol range (< 1.2 mmol/l). None of the HDL parameters measured, either in the fasting or in the postprandial state (HDL cholesterol, HDL triglycerides, HDL GGE subclasses, LpA-I, and LpA-I:A-II), were related to the development of coronary atherosclerosis, whereas the postprandial plasma levels of small chylomicron remnants, which showed weak negative correlations with HDL, related positively to the progression of coronary atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:HDLs and alimentary lipemia. Studies in men with previous myocardial infarction at a young age. 842 32

The effects of two moderate doses of long-chain n-3 fatty acids (3.0 and 4.5 g EPA+DHA per day for 4 weeks each) on serum lipids and lipoproteins of patients with familial combined hyperlipidemia (FCH) were studied in a double-blind, placebo-controlled clinical trial. In nine patients with FCH n-3 fatty acids led to a statistically significant, dose-dependent fall in very low density lipoprotein (VLDL) triglycerides (3 g/day: -42%, 4.5 g/day: -55%) VLDL cholesterol (3 g/day: -41%, 4.5 g/day: -47%), and VLDL apolipoprotein (apo) B-100 (3 g/day: -40%, 4.5 g/day: -56%). No overall change in low-density lipoprotein (LDL) cholesterol was found, as confirmed statistically. However, when analyzing the data of single patients LDL cholesterol and LDL apo B did not change in five patients but increased dose dependently (from pretreatment 4.80 +/- 0.93 mmol/l to 5.70 +/- 0.93 mmol/l LDL cholesterol after 4.5 g/day) in four. LDL and VLDL composition as indicated by cholesterol/apo B-100 and triglyceride/apo B-100 ratios did not change significantly. High-density lipoprotein (HDL) cholesterol was unchanged; the HDL cholesterol/apo A-I+apo A-II ratio increased by 19% (P < 0.05) during fish oil treatment. We conclude that in FCH moderate doses of long-chain n-3 fatty acids are highly effective in lowering pathological VLDL triglycerides, VLDL cholesterol, and VLDL apo B. LDL cholesterol must, however, be monitored during treatment as it may rise substantially in some although not in all patients with this disease.
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PMID:Effects of fish oil concentrate on lipoproteins and apolipoproteins in familial combined hyperlipidemia. 847 18

Lipoprotein metabolism is altered in the majority of patients with renal insufficiency and renal-failure, but may not necessarily lead to hyperlipidemia. The dyslipoproteinemia of renal disease has characteristic abnormalities of the apolipoprotein (apo) profile and lipoprotein composition. It develops during the asymptomatic stages of renal insufficiency and becomes more pronounced as renal failure advances. The qualitative characteristics of renal dyslipoproteinemia are not modified substantially by dialysis treatment. Patients with chronic renal disease may therefore be exposed to dyslipoproteinemia for long periods of time. The characteristic plasma lipid abnormality is a moderate hypertriglyceridemia. The alterations of lipoprotein metabolism affect both the apoB-containing very low-density and intermediate-density, and low-density lipoproteins and the apoA-containing high-density lipoproteins. The main underlying abnormality of lipoprotein transport is a decreased catabolism of the apoB-containing lipoproteins caused by decreased activity of lipolytic enzymes and altered lipoprotein composition. There is an increase of intact or partially metabolized, triglyceride-rich, apoB-containing lipoproteins with a disproportionate elevation of apoC-III and, to a lesser extent, apoE, resulting in a marked increase of the intermediate-density lipoproteins and an enrichment of triglycerides, apoC-III, and apoE in the low-density lipoproteins. In high-density lipoproteins there are decreases in the concentrations of cholesterol, apolipoproteins A-I and A-II, and the high-density lipoprotein-2 to high-density lipoprotein-3 ratio. These abnormalities result in a characteristic decrease of the apoA-I to apoC-III ratio and anti-atherogenic index apoA-I/apoB. The pathophysiologic links between the renal insufficiency and the abnormalities of lipoprotein transport are still poorly defined. Changes in the action of insulin on lipolytic enzymes, possibly mediated via increased levels of parathyroid hormone, have been suggested to play a contributory role. The clinical consequences of a defective lipoprotein transport may be related to the atherogenic character of lipoprotein abnormalities. Renal dyslipoproteinemia may contribute to the development of atherosclerotic vascular disease and progression of glomerular and tubular lesions with subsequent deterioration of renal function. Dietary and/or pharmacologic intervention may ameliorate the uremic dyslipoproteinemia, but the long-term clinical effects of such treatment have yet to be established.
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PMID:Lipoprotein metabolism and renal failure. 850 11

The objective of this study was to determine whether phenolic constituents present in red wine and grape juice modulate plasma lipid and lipoprotein concentrations in healthy human subjects. All subjects consumed in random order 375 ml of red or white wine per day or 500 ml of two different grape juices (high and low phenols) per day for periods of 4 weeks separated by 2-week periods of abstention while continuing normal activity and food intake, and their normal lives in a community setting. The subjects were 24 healthy males aged 26-45 years screened by clinical examination and laboratory tests to exclude hypertension, diabetes mellitus, hyperlipidemia and obesity, among others. Fasting blood was collected at the beginning and end of each beverage schedule for analysis of lipids and lipoproteins. Changes in plasma lipids and lipoproteins in response to each beverage were measured to determine whether these were altered by red wine and grape juice phenolics independently of the effects of ethanol. Both grape juices had virtually no effect. Red and white wines raised plasma HDL-cholesterol and apo A-I and apo A-II concentrations as well as the apo A-I:apo B ratio to a similar extent. Red wine also raised plasma triglyceride and total cholesterol concentrations. Neither wine affected plasma apo B or apo (a) concentrations. The favourable effects of wines in modulating plasma lipid and lipoprotein concentrations are probably due to their alcohol content and cannot be reproduced by grape juices.
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PMID:Wine: does the colour count? 881 66

Lp(a) levels are genetically determined and remain stable without major changes throughout lives. However, when an individual's Lp(a) levels are observed over a one-year period, they show spontaneous variation. The rate of intraindividual variation in Lp(a) was observed in 16 patients with hypertension, hyperlipidemia and/or glucose intolerance in a chronic stable state who regularly visited the hospital clinic once a month, at least 10 times during the year, and in whom a total of 42 blood and clinical chemistry tests including serum lipids, Lp(a) and apoproteins were performed. The rate of annual intraindividual variation of Lp(a) averaged out as 16.6%. The rate was 18.8% for isoform S4 (n = 10), 18.6% for S3 (n = 3), and although small in number of subjects, other isoforms showed minor variation rates. There was a significant negative correlation between the rate of variation (y%) and LP(a) level (xmg/dl) r = -0.605, p < 0.05, y = -0.461 x +29.8). Therefore, when Lp(a) was high, the rate of variation (SD%) was low. This was consistent with the finding that the rates of variation were low for isoforms S2, S3S4 and F, whose molecular weights were low, accompanied by high Lp(a) levels. On the other hand, when the relationship between Lp(a) level and the amount of variation (SD mg/dl) was examined, there was no correlation between the two, since the amounts of variation were almost constant at a level of 3.8 mg/dl, regardless of Lp(a) level. The annual variation of Lp(a) level was found to be related to three groups of factors based on comparison of the variations among WHO phenotypes of hyperlipidemias, univariate correlation analysis with the clinical parameters tested, and multivariate analysis: the first group of factors was related to structure and metabolism of very low-density lipoprotein such as triglycerides, phospholipids, apo C-II, C-III, E, A-II and uric acid; the second group was related to thrombosis centering on platelets; and the third group involved those in the acute phase reactions represented by 1 hr and 2 hr erythrocyte sedimentation rates.
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PMID:Intraindividual variations in lipoprotein (a) levels and factors related to these changes. 922 16

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


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