Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of heparin (bolus e.v. 5.000 I.U.) on blood levels of Lp(a) and other lipids (triglycerides, -HDL, -LDL and total cholesterol, apo A1, apo B100 and apo A1/apo B100) was studied in 15 patients (8 M and 7 F) with chronic renal failure during hemodialysis. Statistically significant reductions of the basal values were found for Lp(a) and the other lipids in the blood taken before the beginning of dialysis, 30 min' after the heparin bolus. The analysis of third blood sample (at the end of the hemodialysis, one hour after the end of the heparin maintenance infusion) showed a rise of HDL and LDL-lipoproteins over the basal values clearly in relation to reduced heparin and plasmatic fraction of the blood. The values of Lp(a) had not so high increase as consequence of more elevated affinity with heparin and of a possible enhanced metabolic rate via lipoprotein lipase. The authors, in agreement with similar changes of Lp(a) and other lipids previously observed in patients with coronary diseases during bypass surgery in extracorporeal circulation or angioplasty, (interventions requiring generous heparin treatment), believe to have now sufficient data for attributing heparin a causal role for the above mentioned effects. The authors stress the needing of other studies better understand the action to mechanisms of heparin and to evaluate possible future clinical applications of this new interesting Lp(a)-clearing effect.
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PMID:[Heparin and lipoprotein(a). Observations during hemodialysis]. 810 96

We found a significantly reduced incidence of increased lipoprotein(a) (Lp(a)) levels in subjects with triglycerides (TG) greater than 150 mg/dl compared with those with TG levels lower than 150 mg/dl. This was the case in patients with angiographically documented coronary artery disease (CAD) and in subjects with no CAD. We explored the potential role of lipoprotein lipase (LPL) in mediating this relationship. Lp(a) and LDL2 exhibited a minimal effect on the rate constant for degradation of VLDL-TG by LPL (13% inhibition). Binding analyses indicated no differences between VLDL and LDL with respect to Lp(a) binding, and lipolysis only reduced binding by 30% at 75% degradation of VLDL-TG. Our study indicates that the inverse relationship between elevated plasma TG and Lp(a) levels is not caused by activation of LPL by Lp(a) either due to failure of Lp(a) to bind to VLDL or its lipolytic remnants. It is hypothesized that this relationship could stem from the enhanced clearance of TG-rich lipoproteins in individuals with higher levels of Lp(a) by receptor-mediated events.
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PMID:Triglyceride-rich lipoprotein interactions with Lp(a). 818 4

A one-point cross-sectional study of 20 sedentary individuals, 20 low-aerobic athletes (body-builders), and 20 high-aerobic athletes (long distance, endurance runners) was conducted in Mexico City, Mexico to determine the influence of these diverse life-styles on the plasma levels of Lp(a). Only non-obese male subjects, aged 23-33, who were nonsmokers, non-alcoholics, and had never used anabolic steroids were included in this study. Blood samples were drawn 24 h following the last period of physical activity, and after a 12-14-h fast-period and a 15-min sitting-rest. Plasma levels of Lp(a) and other parameters, including postheparin lipoprotein lipase (LPL) and hepatic lipase (HL) activities, triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), as well as % body fat and muscle mass, and maximum aerobic capacity (VO2max) were measured to determine possible correlations with Lp(a) and to serve as convenient internal standards. Mean Lp(a) concentrations were significantly higher in the runners (52 +/- 19 mg/dl) than in the body-builders (40 +/- 6.4 mg/dl, P < 0.05) and the sedentary subjects (24 +/- 5 mg/dl, P < 0.001). Positive correlations between Lp(a) and Vo2max (P < 0.001), HDL-C (P < 0.005) and HDL2-C subfraction (P < 0.005), and a negative correlation with TG were determined. Agglomerative cluster methods suggested three close-distance clusters and a fourth cluster which is composed of four runners who exhibited low LDL-C/HDL-C and high LPL/HL ratios, high mean Lp(a), HDL2-C, and Vo2max levels, but low TG levels. These data show that some individuals who maintain a life-style of very high level physical exertion may have remarkably elevated plasma Lp(a) concentrations. The highly increased concentrations of Lp(a) in high exercise athletes may represent a normal metabolic response to repeated small tissue injuries resulting from frequent and prolonged large muscle movement.
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PMID:Long distance runners and body-builders exhibit elevated plasma levels of lipoprotein(a). 818 16

The genetic and environmental determinants of hypertension, lipid abnormalities, and coronary artery disease (CAD) have been studied for 15 years in Utah in population-based multigenerational pedigrees (2500 subjects among 98 pedigrees), twin pairs (74 monozygous and 78 dizygous), hypertensive siblings (131 sibships), siblings with CAD before age 55 (45 sibships), and anecdotally ascertained pedigrees with type II diabetes (271 subjects among 16 pedigrees), lipoprotein lipase deficiency (106 subjects in a single pedigree), and familial hypercholesterolemia (502 heterozygotes among 50 pedigrees). Estimates of heritability ranged from 20 to 75% for blood pressures and blood lipids. A strong positive family history predicts a future occurrence of hypertension (relative risk [RR] = 3.8) and CAD (RR = 12.7). Segregating single-gene effects were found for several 'intermediate phenotypes' associated with hypertension (erythrocyte sodium-lithium countertransport, intraerythrocytic sodium, a relative fat pattern, total urinary kallikrein excretion, and fasting insulin levels). Strong single-gene effects in segregation analysis were also found for low-density lipoprotein (LDL) cholesterol, lipoprotein (a) (Lp[a]), low high-density lipoprotein (HDL) cholesterol, and high apolipoprotein (apo) B. Deoxyribonucleic acid (DNA) markers of lipid abnormalities or hypertension have included LDL-receptor defects, lipoprotein lipase deficiency, high Lp(a), familial defective apo B, decreased quantitative levels of apo B, apo E phenotype, angiotensinogen, and 'glucocorticoid remediable aldosteronism (GRA) hypertension.' Also tested in Utah studies, but not found to be DNA markers for hypertension, were the genetic loci for the structural genes for renin and angiotensin-converting enzyme, and the sodium antiport system. In addition, important gene-gene interactions (LDL receptor with apo E2) and gene-environment interactions (kallikrein with potassium intake) were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. 829 39

Prominent features of atheromata include smooth muscle cells, cholesteryl ester-loaded macrophage foam cells, extracellular matrix, extracellularly trapped and aggregated lipoproteins, and various enzymes including lipoprotein lipase (LpL) and sphingomyelinase (SMase). The interplay of these factors was investigated in cell culture. Incubation of bovine aortic smooth muscle cells for 18 h at 37 degrees C with low density lipoprotein (LDL) in the presence of LpL and SMase led to massive aggregation of LDL on the surface of the cells as viewed by phase, fluorescence (using 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate-LDL), and electron microscopy. This aggregation required both enzymes. Studies with 125I-LDL confirmed these observations: 125I-LDL cell association in the presence of LpL plus SMase was 50-100-fold greater than in the absence of the two enzymes and was 10-fold greater than in the presence of either enzyme alone. A similar effect (68-fold enhancement) was seen with 125I-labeled lipoprotein(a) (Lp(a)), another atherogenic lipoprotein. In all cases, 125I-lipoprotein degradation was relatively low (< 5% of cell-associated material). LpL/SMase-mediated association of 125I-LDL with smooth muscle cells was still observed when enzymatically inactive LpL was used. The effect was markedly diminished when the smooth muscle cells were treated with a combination of chondroitin ABC lyase and heparitinase or when mutant Chinese hamster ovary cells that lack cell-surface proteoglycans were used, indicating a specific role for cellular proteoglycans. When smooth muscle cells with 125I-LDL or 125I-Lp(a) aggregates were rinsed and then coincubated with mouse peritoneal macrophages for a further 24 h, visible aggregates disappeared, and there was marked 125I-lipoprotein degradation. Electron micrographs after 24 h of co-culture showed lipid-laden, foamy macrophages situated on top of smooth muscle cells, suggesting that the macrophages phagocytosed and metabolized the smooth muscle cell-associated LDL aggregates. Last, 125I-LDL association with smooth muscle cell extracellular matrix was also synergistically enhanced by LpL and SMase, to a level that was 19-fold greater than in the absence of the two enzymes. Thus, the interaction of LDL and Lp(a) with four atheroma components, namely, smooth muscle cells, extracellular matrix, LpL, and SMase, represents a physiologically plausible mechanism for massive, focal retention and aggregation of atherogenic lipoproteins in the arterial wall with subsequent macrophage foam cell formation.
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PMID:Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix. A possible mechanism for low density lipoprotein and lipoprotein(a) retention and macrophage foam cell formation. 837 99

The relationship between lipoprotein(a) [Lp(a)] and metabolism of triglyceride-rich lipoproteins (TRL) was studied in 58 untreated patients with familial combined hyperlipidemia (FCH) from eight different kindreds, 17 spouse controls, and 17 unrelated controls. Lp(a) plasma concentrations were not significantly different between FCH subjects (343 +/- 61 mg/L, mean +/- SEM) and controls (249 +/- 52 mg/L). In FCH, log-transformed Lp(a) levels correlated positively with postheparin lipoprotein lipase ([LPL] r = .61, P = .0002) and hepatic lipase ([HL] r = .46, P = .008) activities and total plasma cholesterol level (r = .30, P = .03). In controls, Lp(a) correlated with LPL (r = .50, P = .04) and total plasma cholesterol level (r = .51, P = .003). In eight FCH patients, treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin resulted in significantly increased mean LPL activities and plasma Lp(a) concentrations. In three of these FCH patients, repeated measurements during 1 year demonstrated that changes in Lp(a) concentrations were paralleled by similar changes in LPL activity, but not HL activity. The observed correlation between postheparin plasma lipolytic activities and Lp(a) plasma concentrations suggests a connection between the metabolism of TRL and Lp(a).
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PMID:Lipoprotein(a) plasma concentrations associated with lipolytic activities in eight kindreds with familial combined hyperlipidemia and normolipidemic subjects. 851 May 21

Recombinant human growth hormone (GH) administered as daily subcutaneous (SC) injections has been shown to affect serum lipoproteins in GH-deficient subjects. However, the effects of continuous infusion of GH on serum lipoproteins have not been investigated in GH-deficient adults. The aim of the present study was to compare effects of daily injections and continuous infusion of GH on lipoprotein metabolism. Recombinant human GH (0.25 U/kg/wk) was administered to nine GH-deficient adult men during a period of 14 days in two different ways, ie, as a daily SC injection at 8:00 PM and as a continuous SC infusion, with 1 month of washout between the treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. Abdominal SC adipose tissue lipoprotein lipase (LPL), postheparin plasma LPL, and hepatic lipase (HL) activity were measured 120 minutes after the intake of 100 g glucose. Adipose tissue LPL activity decreased and postheparin plasma HL activity increased after 14 days of GH treatment irrespective of the mode of GH administration, whereas GH treatment had no effect on postheparin plasma LPL activity. Serum triglyceride and very-low-density lipoprotein (VLDL) triglyceride concentrations increased during GH treatment. However, VLDL triglyceride concentrations increased to a greater degree during treatment with daily GH injections than during continuous infusion of GH. Serum apolipoprotein (apo) B and low-density lipoprotein (LDL) cholesterol concentrations decreased during treatment with daily GH injections, but were not significantly affected by continuous GH infusion. Thus, apo B and LDL cholesterol concentrations were lower after daily GH injections versus continuous GH infusion. Serum lipoprotein(a) [Lp(a)] and apo E concentrations increased during both modes of GH treatment. However, continuous infusion of GH resulted in a more marked increase in Lp(a) and apo E concentrations than daily GH injections. Minor effects were observed on serum apo A-I concentrations but high-density lipoprotein (HDL) cholesterol concentrations were not affected. In conclusion, GH treatment of GH-deficient men influenced adipose tissue LPL and postheparin plasma HL activity, as well as serum lipoprotein concentrations. Moreover, continuous GH infusion and daily GH injections differed with respect to the magnitude of effects on several lipoprotein fractions including VLDL triglycerides, LDL cholesterol, apo B, apo E, and Lp(a) concentrations.
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PMID:Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. II. Effects on serum lipoproteins and lipoprotein and hepatic lipase activity. 860 46

Two common coding sequence mutations of lipoprotein lipase (serine447-ter, producing a carboxy terminal truncation; and asp9-asn variants) were studied in 329 Caucasian subjects, of whom 243 had angiographic features of premature atheroscelerosis (220 with coronary artery disease; 23 with coronary and peripheral artery disease). As expected, the mean levels of cholesterol, triglycerides, LDL-cholesterol, ApoB and Lp(a) were significantly higher in the arterial disease group than in the controls. HDL levels were lower in the patient group. With regard to the common mutations, plasma triglycerides and VLDL-triglycerides were lower in subjects possessing the Serine447-Ter mutation (p = 0.06 and < 0.05, respectively). When the lipid distributions were analysed by tertiles, the Ser447-Ter mutation was significantly less frequent in the highest tertiles for triglycerides (p < 0.02), and VLDL (p < 0.04). The Asp9-Asn substitution was significantly more frequent in the lowest tertiles for ApoAI (p = 0.05). Case-control analyses of genotypic distributions between the two groups with or without arterial disease did not show any significant differences. The possible functional effects of these common mutants of lipoprotein lipase are discussed.
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PMID:Common genetic variants of lipoprotein lipase that relate to lipid transport in patients with premature coronary artery disease. 883 23

Recently, it has been recognized that cell-bound heparan sulfate (HS) proteoglycans (HSPG) are able to bind and subsequently initiate degradation of lipoproteins. Two mediators of lipoprotein catabolism, both with HS binding capacity, lipoprotein lipase (LPL) and apolipoprotein E (apoE), are involved in this process. This mechanism is known as the secretion-capture process of apoE. Lipoprotein(a) [Lp(a)] was shown to have a strong binding capacity to cell-associated HSPG. This binding capacity was increased by LPL addition. We investigated the effects of recombinant apoE (r-apoE) enrichment of Lp(a) on the binding to HS. Lp(a), isolated by ultracentrifugation and gel filtration, was incubated with r-apoE and reisolated by ultracentrifugation, resulting in r-apoE-enriched Lp(a). ApoE-enriched Lp(a) and control Lp(a) were coated to microtiter plates. The capacity to bind biotin-conjugated HS (b-HS) in the presence or absence of inactivated bovine LPL was studied. R-apoE-enriched Lp(a) showed increased b-HS binding capacity versus control Lp(a). Addition of LPL resulted in an increased b-HS binding capacity of both control and r-apoE-enriched Lp(a). To investigate whether binding of Lp(a) to endothelial cell HSPG occurred in vivo, 39 volunteers were injected with heparin (50 U/kg) and plasma lipid and Lp(a) levels were determined before and 20 minutes after heparin injection. No significant increase in plasma Lp(a) concentrations was found. The results showed that Lp(a) can be enriched with apoE and that this resulted in increased LPL-enhanced binding to HSPG. From the in vitro studies, it can be concluded that the secretion-capture process of apoE is a possible catabolic route for Lp(a). However, whether this also occurs in vivo remains to be confirmed.
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PMID:Lipoprotein lipase-enhanced binding of lipoprotein(a) [Lp(a)] to heparan sulfate is improved by apolipoprotein E (apoE) saturation: secretion-capture process of apoE is a possible route for the catabolism of Lp(a). 918

We have identified a kindred in Providence, RI, deficient in hepatic triglyceride lipase (HL). The two affected brothers have coronary heart disease and elevated levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein [apo] A-I. The lipoprotein lipase (LPL) activity is normal. We and others have postulated that the effects of oral anabolic steroids on HDL metabolism are mediated by HL. To test this hypothesis, we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL2 cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II. Although stanozolol failed to induce HL activity in the HL-deficient man, HDL cholesterol, HDL2 cholesterol, and apo A-I were reduced a mean of 20%, 48%, and 32%, respectively. In contrast to controls, HDL3 cholesterol (46%) and apo A-II (14%) increased in HL-deficient subjects. Stanozolol treatment also increased LPL activity (124% +/- 86%, n = 4) and decreased lipoprotein(a) ([Lp(a)] 66% +/- 3%, n = 3) in the three men with detectable levels. The data indicate that in addition to stimulation of HL activity, stanozolol treatment changes HDL cholesterol concentration and subfraction distribution by other mechanisms.
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PMID:Effects of short-term stanozolol administration on serum lipoproteins in hepatic lipase deficiency. 928 85


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