Biomedical subjects

H Jansen

Publications and source records attributed to H Jansen.

At least 55 records · Page 3Linked to original sources

PubMed1998

Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotein lipase activity.

The acute effects of intravenous heparin administration (50 U/kg body weight) on apolipoprotein (apo)B-48 and apoB-100-containing lipoproteins in relation to postheparin lipase activities were studied in ten healthy normolipidemic volunteers. Five subjects returned to receive sham injections with saline. Lipoproteins were separated from plasma by density gradient ultracentrifugation at baseline, 3, and 20 min postheparin. ApoB-48 and apoB-100 in d < 1.006 g/mL and 1.006 < d < 1.019 g/mL fractions were quantitatively measured after electrophoresis on 5% SDS polyacrylamide gels and Coomassie-blue staining. No significant changes were observed after saline injections. Heparin administration released lipoprotein lipase (LPL) and hepatic lipase (HL) activities after 20 min, and significantly reduced apoB-48 concentrations in d < 1.006 g/mL fractions only. ApoB-100 concentrations showed a trend to decrease in d < 1.006 g/mL fractions and to increase in 1.006 < d < 1.019 g/mL fractions. LPL activity was related to the percentual disappearance of apoB-48 (r = 0.81, P = 0.004) and apoB-100 (r = 0.91, P < 0.001) in d < 1.006 g/mL fractions. When little LPL was released (LPL activity < 120 mU/mL) by heparin, apoB-48 was preferentially eliminated over apoB-100. However, when abundant LPL was released (LPL activity > 140 mU/mL), comparable percentual reductions for apoB-48 and apoB-100 were seen. Pharmacokinetic analysis revealed first-order kinetics for the clearance of apoB-48 in d < 1.006 g/mL fractions, but zero-order kinetics for apoB-100 clearance. Under conditions of artificially enhanced lipolysis, the first catabolic step of apoB-48-containing lipoproteins and hepatic VLDL showed different pharmacokinetics. ApoB-48-containing lipoproteins were the preferred substrate for LPL, and only when abundant LPL was present, clearance of hepatic VLDL occurred.

Adolescent↗

PubMed1998

The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia.

OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION: Acipimox in a daily dose of 3 X 250 mg for 12 weeks. MAIN OUTCOME MEASURES: Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification. RESULTS: Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG > 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+ 15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but none of these changes reached the level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels. HDLc was also significantly improved.

Adult↗

PubMed1997

Human lactoferrin receptor activity in non-encapsulated Haemophilus influenzae.

Since the ability of bacteria to compete with lactoferrin for iron contributes to the pathogenesis of mucosal infections, the presence of lactoferrin receptor activity in non-encapsulated Haemophilus influenzae was investigated. The growth of 18 H. influenzae isolates from the sputum samples of chronic bronchitis patients and of six of seven H. influenzae throat isolates from healthy adults was stimulated by iron saturated human lactoferrin. Apo-lactoferrin did not stimulate the growth of H. influenzae. Human lactoferrin binding to iron limited bacteria was detected for 16 H. influenzae strains from chronic bronchitis patients and for five of seven isolates from healthy adults. We conclude that the majority of H. influenzae isolates tested bind human lactoferrin and that the iron from lactoferrin is used for growth.

Adult↗

PubMed1997

Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group.

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the lipolysis of triglyceride-rich lipoproteins, and the gene coding for LPL is therefore a candidate gene in atherogenesis. We previously demonstrated that two amino acid substitutions in LPL, the Asn291-Ser and the Asp9-Asn, are associated with elevated triglycerides and lower HDL cholesterol and are present with greater frequency in coronary artery disease (CAD) patients than in normolipidemic control subjects. Conversely, a third frequent mutation in this gene, the Ser447-Stop, is reported by some investigators to underlie higher HDL cholesterol levels and would represent a beneficial genetic variant in lipoprotein metabolism. We therefore sought conclusive evidence for these allegations by investigating the effects of the LPL Ser447-Stop mutation on LPL and hepatic lipase (HL) activity, HDL cholesterol, and triglycerides in a large group of CAD patients (n = 820) with normal to mildly elevated total and LDL cholesterol levels. METHODS AND RESULTS: Carriers of the Ser447-Stop allele (heterozygotes and homozygotes) had significantly higher postheparin LPL activity (P = .034), normal postheparin HL activity (P = .453), higher HDL cholesterol levels (P = .013), and lower triglyceride levels (P = .044) than noncarriers. The influence of the Ser447-Stop allele on LPL activity was pronounced in patients using beta-blockers (P = .042) and not significant in those not using them (P = .881), suggesting a gene-environment interaction between the Ser447-Stop mutation and beta-blockers. CONCLUSIONS: We conclude that the LPL Ser447-Stop mutation has a significant positive effect on LPL activity and HDL cholesterol and triglyceride levels and that certain subgroups of CAD patients carrying the Ser447-Stop mutation will have less adverse metabolic effects when placed on beta-blockers. The LPL Ser447-Stop mutation therefore should have a protective effect against the development of atherosclerosis and subsequent CAD.

Adrenergic beta-Antagonists↗

PubMed1997

Growth hormone restores hepatic lipase mRNA levels but the translation is impaired in hepatocytes of hypothyroid rats.

During hypothyroidism, hepatic lipase (HL) activity is decreased. The low HL may be due to thyroid hormone insufficiency or to the concomitant fall in growth hormone (GH) activity. We studied HL expression in hepatocytes freshly isolated from hypothyroid rats with and without additional GH-substitution. In all animals HL mRNA was detected by RT-PCR in the hepatocytes, but not in the non-parenchymal cells. In hypothyroid cells HL mRNA levels were reduced by 40%, and the in vitro secretion of HL-activity and HL-protein was decreased by about 50%. In cells from GH-substituted hypothyroid rats, HL mRNA level was normalised, but the secretion of HL remained low. The specific enzyme activity of secreted HL was similar under all conditions. The discrepancy between HL mRNA and HL secretion in GH-supplemented rats may be due to (post)translational effects. Therefore we studied the HL synthesis and maturation in hepatocytes from hypothyroid and GH-substituted rats. Pulse-labelling experiments with [(35)S]methionine showed that the incorporation of [(35)S]methionine into HL protein was lower both in hypothyroid cells and in GH-supplemented cells than in control cells. During the subsequent chase, the intracellular processing and transport of newly synthesized HL protein in the hepatocytes from hypothyroid rats, whether or not supplemented with GH, was similar to control cells. We conclude that in livers of hypothyroid, GH-substituted rats translation of HL mRNA is inhibited despite restoration of HL mRNA levels.

Animals↗

PubMed1997

Hepatic lipase is localized at the parenchymal cell microvilli in rat liver.

Hepatic lipase (HL) is thought to be located at the vascular endothelium in the liver. However, it has also been implicated in the binding and internalization of chylomicron remnants in the parenchymal cells. In view of this apparent discrepancy between localization and function, we re-investigated the localization of HL in rat liver using biochemical and immunohistochemical techniques. The binding of HL to endothelial cells was studied in primary cultures of rat liver endothelial cells. Endothelial cells bound HL in a saturable manner with high affinity. However, the binding capacity accounted for at most 1% of the total HL activity present in the whole liver. These results contrasted with earlier studies, in which non-parenchymal cell (NPC) preparations had been found to bind HL with a high capacity. To study HL binding to the different components of the NPC preparations, we separated endothelial cells, Kupffer cells and blebs by counterflow elutriation. Kupffer cells and endothelial cells showed a relatively low HL-binding capacity. In contrast, the blebs, representing parenchymal-cell-derived material, had a high HL-binding capacity (33 m-units/mg of protein) and accounted for more than 80% of the total HL binding in the NPC preparation. In contrast with endothelial and Kupffer cells, the HL-binding capacity of parenchymal cells could account for almost all the HL activity found in the whole liver. These data strongly suggest that HL binding occurs at parenchymal liver cells. To confirm this conclusion in situ, we studied HL localization by immunocytochemical techniques. Using immunofluorescence, we confirmed the sinusoidal localization of HL. Immunoelectron microscopy demonstrated that virtually all HL was located at the microvilli of parenchymal liver cells, with a minor amount at the endothelium. We conclude that, in rat liver, HL is localized at the microvilli of parenchymal cells.

Animals↗

PubMed1997

Hepatic lipase gene expression is transiently induced by gonadotropic hormones in rat ovaries.

Hepatic lipase (HL) gene expression was studied in rat ovaries. A transcript lacking exons 1 and 2 could be detected by reverse transcription-polymerase chain reaction (RT-PCR) in the ovaries of mature cyclic females and of immature rats treated with pregnant mare serum followed by human chorionic gonadotropin (hCG) to induce superovulation. By competitive RT-PCR the HL transcript was quantified. Low levels of HL mRNA were detected in ovaries of mature cyclic females and of immature rats. During superovulation HL mRNA was several fold higher than in mature cyclic rats and transiently increased to a maximum at 2 days after hCG treatment. Pulse-labelling of ovarian cells and ovarian slices with [35S]methionine followed by immunoprecipitation with polyclonal anti-HL IgGs showed de novo synthesis of a 47 kDa HL-related protein. Expression of the protein was transiently induced by gonadotropins with a peak at 2 days after hCG treatment. Induction of liver-type lipase activity occurred only after HL mRNA and synthesis of the HL-related protein had returned to pre-stimulatory levels. We conclude that in rat ovaries the HL gene is expressed into a variant mRNA and a 47 kDa protein. The expression of the HL gene in ovaries is inducible and precedes the expression of the mature, enzymatically active liver-type lipase.

Animals↗

PubMed1997

Acute effects of adrenaline on hepatic lipase secretion by rat hepatocytes.

Catecholamines are responsible for the daily changes in hepatic lipase (HL) expression associated with feeding and fasting. We have studied the mechanism by which adrenaline decreases HL secretion in suspensions of freshly isolated rat hepatocytes. Adrenaline acutely inhibited HL activity through activation of the alpha1-adrenergic pathway. The cells had significantly less HL activity in the presence of adrenaline versus cycloheximide, where protein de novo synthesis is completely blocked. The specific enzyme activity of secreted HL was not affected. Intracellular HL activity was decreased by adrenaline treatment. Pulse-labeling with [35S]methionine showed that de novo synthesis of the 53-kd endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive HL protein was unaffected by adrenaline. During subsequent chase of the control cells, the 53-kd form was converted to a 58-kd Endo H-resistant HL protein, which was rapidly secreted into the medium. In the presence of adrenaline, formation of the 58-kd protein was markedly reduced, whereas the 53-kd protein disappeared at a rate similar to the rate in controls. This suggests that part of the HL protein was degraded. In contrast to adrenaline, inhibition of HL secretion by colchicine was accompanied by an intracellular accumulation of HL activity and of the 58-kd protein. We conclude that adrenaline inhibits HL secretion posttranslationally by retarding the maturation of the 53-kd HL precursor to an active 58-kd protein, possibly by stimulating degradation of newly synthesized HL protein.

Animals↗

PubMed1997

Conversion from cyclosporine A to azathioprine treatment improves LDL oxidation in kidney transplant recipients.

The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has been associated with less favorable plasma lipid profiles, which may contribute to the high incidence of cardiovascular morbidity and mortality in transplant recipients. Recent studies have suggested that oxidative modification of LDL plays an important role in the initiation and progression of atherosclerosis. It has also been demonstrated that CsA may facilitate lipid peroxidation in vitro and in vivo. Therefore, we determined several parameters of LDL oxidizability in renal transplant recipients who were switched from CsA to azathioprine (AZA)-based immunosuppressive treatment. The susceptibility of LDL to in vitro oxidation, LDL particle size, plasma titers of IgG and IgM antibodies against oxidized LDL and plasma LDL subclass patterns in 19 renal transplant recipients were determined during CsA treatment and 16 weeks after these patients were converted to AZA treatment. In addition, mean arterial pressure was recorded, and glomerular filtration rate and renal blood flow were estimated from the clearance of radiolabeled thalamate and hippurate. After conversion, the plasma concentrations of total cholesterol, LDL cholesterol and triglyceride decreased, while plasma HDL cholesterol did not change. During CsA therapy plasma LDL was significantly more susceptible to in vitro oxidation than during AZA, as reflected by a longer lag phase during in vitro oxidation (98.9 +/- 24.3 vs. 114.7 +/- 17.3 min, P = 0.031). In addition, the LDL size increased (236.5 +/- 7.3 vs. 240.7 +/- 6.8 nm, P = 0.00001), and the titers of IgM- and IgG-autoantibodies against oxidized LDL decreased significantly after patients were converted from CsA to AZA. The more atherogenic LDL subclass pattern B was present in 13 out of 19 patients during CsA. In five patients, pattern B changed into pattern A after conversion. The subclass B pattern was maintained in eight patients and subclass A pattern in six patients. In all patients the lag time of in vitro LDL oxidation increased, although the biggest changes were found in those patients in whom the LDL subclass changed from pattern B to pattern A. Mean arterial pressure decreased and renal function improved significantly after conversion. No correlation between parameters of lipid peroxidation and changes in blood pressure or renal function upon conversion, underlying renal disease, time since transplantation, or antihypertensive treatment was found. Our study demonstrates that treatment with CsA increases the susceptibility of LDL to in vitro oxidation, and also enhances the oxidation of LDL in vivo. In addition, conversion to AZA results in a more favorable lipid profile, which in combination with a lower arterial pressure and better renal function may decrease the risk for atherosclerosis. These factors may account for the cardiovascular complications during CsA treatment after organ transplantation, and also when CsA is used for other diseases.

Adolescent↗

PubMed1997

Transient hyperlipidemia during treatment of ALL with L-asparaginase is related to decreased lipoprotein lipase activity.

A 13-year-old girl with acute lymphoblastic leukemia (ALL) developed extremely high plasma triglyceride (TG) concentrations of 103 mmol/l (reference value <1.8 mmol/l) during combination treatment with corticosteroids and asparaginase. Corticosteroids are known to induce the production of TG-rich particles. On the other hand, corticosteroids increase the activity of lipoprotein lipase (LPL), a key enzyme in the removal of TG from plasma. Generally, the increased LPL activity prevents an extreme rise in TG levels upon therapy with corticosteroids. In our patient, we found that the corticosteroid-induced LPL activity dramatically declined after therapy with L-asparaginase. This suggests that the extensive hypertriglyceridemia in our patient was due to an L-asparaginase-induced decrease in LPL activity. This hypothesis was further supported by the finding that hypertriglyceridemia was less severe when corticosteroids and asparaginase were given separately.

Adolescent↗

PubMed1997

Supracondylar fractures of the femur treated by external fixation.

OBJECTIVE: To determine the results and complications of treating supracondylar fractures of the femur with external fixation. DESIGN: Retrospective follow-up from the time of injury (inception cohort) to an average of thirty-one (range thirteen to seventy-two) months after injury. SETTING: Tertiary care university hospital. PATIENTS: All thirteen adult patients with supracondylar femur fractures treated with the method described were included. There were seven closed and five open fractures and five vascular injuries that required repair. Fractures were chosen for this technique on an individual basis by the treating surgeon. INTERVENTIONS: The femoral condyles were reduced percutaneously or via a medial arthrotomy and stabilized with 6.5-millimeter cannulated screws. Fixator pins were placed from lateral to medial in the condyles and in the shaft above the fracture. The monolateral fixator was applied laterally and stabilized the reduced condyles to the shaft. Initial grafts of bone were used in five fractures. External fixation time averaged 127 days. OUTCOME MEASURES: During treatment we determined the occurrence of complications at the pin sites and the fracture site, the time of healing, and the angular alignment at healing. At the latest follow-up we determined the range of motion of the knee, knee stability, a standardized knee score, and on radiographs the occurrence of arthrosis. RESULTS: Twelve fractures healed primarily. One patient had a fracture site infection and required further treatment before healing. Knee flexion was restricted while in the fixator but rapidly recovered after frame removal. At follow-up (average thirty-one months), the range of knee flexion averaged 111 degrees (range sixty-five to 140). The Iowa Knee Score averaged 87 points (range 75-93 points). Four femurs healed with angular malalignments, shortening, or both. Twelve knees had no detectable arthrosis. CONCLUSIONS: We concluded that in select supracondylar femur fractures, monolateral external fixation is a satisfactory treatment alternative.

Adolescent↗

PubMed1997

Hepatic lipase gene polymorphisms influence plasma HDL levels. Results from Finnish EARS participants. European Atherosclerosis Research Study.

Hepatic lipase (HL), a triglyceride lipase found in liver, adrenals, testes, and ovaries, takes part in the uptake, remodeling, and function of lipoproteins including HDL, as well as VLDL and chylomicrons. In the present study, the genotype distribution of five HL polymorphisms (-C480T, V133V, T202T, L334F, T457T) and their association to plasma lipid values were investigated. The study participants included 92 students with paternal history of myocardial infarction before the age of 55 and 194 matched control subjects, ie, the Finnish participants of the European Atherosclerosis Research Study (EARS). The allele T of the HL polymorphism -C480T showed an association with elevated HDL, apoA-I, and LpA-I values (ANOVA P < .01). No difference in genotype distribution was observed in the offspring with and without paternal history of myocardial infarction.

Adolescent↗

PubMed1997

Common C-to-T substitution at position -480 of the hepatic lipase promoter associated with a lowered lipase activity in coronary artery disease patients.

We studied the molecular basis of low hepatic lipase (HL) activity in normolipidemic male patients with angiographically documented coronary artery disease (CAD). In 18 subjects with a lowered HL activity (< 225 mU/mL), all nine exons of the HL gene and part of the promoter region (nucleotides -524 to +7) were sequenced. No structural mutations in the coding part of the HL gene were found, but 50% of the subjects showed a C-to-T substitution at nucleotide -480. Screening for the base substitution in 782 patients yielded an allele frequency of 0.213 (297 heterozygotes, 18 homozygotes). In a group of 316 nonsymptomatic control subjects, the allele frequency was 0.189, which is significantly less than in the CAD patients (P = .035). In the CAD patients, the C-to-T substitution was associated with a lowered lipase activity (heterozygotes -15%, homozygotes -20%). The patients were divided into quartiles on the basis of HL activity. Sixty percent (allele frequency 0.32) of the patients in the lowest quartile (HL activity < 306 mU/mL) had the gene variant against 27% (allele frequency 0.14) in the highest quartile (HL activity > 466 mU/mL). In the noncarriers, but not in the carriers, HL activity was related with plasma insulin, being increased at higher insulin concentration. Homozygous carriers had a significantly higher HDL cholesterol level-than noncarriers (1.13 +/- 0.28 mmol/L versus 0.92 +/- 0.22 mmol/L, P < .02). Our results show that a C-to-T substitution at -480 of the HL promoter is associated with a lowered HL activity. The base substitution, or a closely linked gene variation, may contribute to the variation in HL activity and affect plasma lipoprotein metabolism.

Alleles↗

PubMed1997

Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males.

This report describes the association between a frequent mutation in the lipoprotein lipase (LPL) gene and HDL cholesterol levels. It concerns a previously described defect that predicts a premature truncation of the LPL protein (447stop). We determined the frequency of this mutation in three groups of healthy men with low-, middle-, and upper-decile HDL cholesterol. The number of carriers of the 447stop allele was significantly greater in the high HDL group than in either the groups with normal HDL (P = .017) or low HDL (P < .0001). Additional functional assessment of this mutation did not reveal distinct differences between wild-type LPL and the LPL447stop protein. In conclusion, we have shown that the 447stop mutation is associated with increased HDL cholesterol in healthy Dutch males, although the underlying mechanism remains to be elucidated. Because HDL cholesterol is strongly inversely related with CAD, this genotype might be of potential benefit to its carriers.

Adult↗

PubMed1997

Iron-binding proteins in sputum of chronic bronchitis patients with Haemophilus influenzae infections.

Airway inflammation during infection is associated with increased transudation of serum proteins and increased production of protein by the airway epithelium. We therefore, assessed whether Haemophilus influenzae infections in patients with chronic bronchitis are associated with increased levels of transferrin and lactoferrin in the sputum compared to uninfected patients. Sputum sol phase and serum samples from 14 infected and 13 uninfected patients with chronic bronchitis and from 12 bronchial asthma patients were included in the study. The median Q-values (the concentration in sputum sol phase/the concentration in serum) x 10(3) of transferrin appeared increased in chronic bronchitis patients with an H. influenzae infection (26.0, n=13) compared to uninfected controls (9.5, n=11) and bronchial asthma patients (4.5, n=6). The ratio of the Q(transferrin)/Q(albumin) was >1 in infected chronic bronchitis patients, indicating local production of transferrin. Growth of H. influenzae was stimulated more in sputum from infected and uninfected patients with chronic bronchitis than in sputum from patients with bronchial asthma. The concentrations of lactoferrin were not significantly different in infected (n=14) and uninfected (n=13) chronic bronchitis patients and bronchial asthma patients (n=12) (median 137.4, 84.6, 87.1 mg x L(-1), respectively). We conclude that in patients with chronic bronchitis with Haemophilus influenzae infections, the levels of transferrin are increased and the levels of lactoferrin are not associated with infections.

Adult↗

PubMed1997

The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia.

OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION: Acipimox in a daily dose of 3 x 250 mg for 12 weeks. MAIN OUTCOME MEASURES: Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification. RESULTS: Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG < 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but non of these changes reached the level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels, HDLc was also significantly improved.

Adult↗

PubMed1996

The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis. REGRESS Study Group, Interuniversity Cardiology Institute, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study.

BACKGROUND: Many patients suffering from premature coronary artery disease report a family history for such events. A mutation in a particular gene, which confers susceptibility for atherosclerosis, will be found more frequently in individuals suffering from coronary atherosclerosis than in the general population. We have recently reported the identification of an Asp9 Asn substitution in the lipoprotein lipase (LPL) enzyme. We analyzed the impact of this mutation on the progression of coronary atherosclerosis and the effect of pravastatin in both carriers and noncarriers. METHODS AND RESULTS: All patients were enrolled in the quantitative coronary angiographic clinical trial REGRESS, which studied the impact of pravastatin therapy on coronary atherosclerosis. The Asp9 Asn mutation was identified in 38 of 819 (4.8%) patients. Carriers of the mutation more often had a positive family history of cardiovascular disease and lower HDL cholesterol levels than noncarriers. In the placebo group, carriers showed more progression of coronary atherosclerosis than noncarriers: mean reduction of the minimum obstruction diameter of -0.25 mm versus -0.12 mm (P = .029) and increase of percentage diameter stenosis of 6.4% versus 1.4% (P = .004). Moreover, the adjusted relative risk for a clinical event for carriers was calculated at 2.16 (95% CI, 1.09 to 4.29; P = .027). Although the lipid-lowering effect of pravastatin was attenuated in carriers, it appeared that these patients showed a response similar to noncarriers in terms of less progression of atherosclerosis and event-free survival. CONCLUSIONS: This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event-free survival.

Amino Acid Sequence↗

PubMed1996

Functional molecular mass of rat hepatic lipase in liver, adrenal gland and ovary is different.

Lipoprotein lipase (LPL) is functionally active only as a dimer. It is also generally assumed that the highly homologous hepatic lipase functions as a dimer, but no clear evidence has been presented. A hepatic lipase-like activity, also indicated as L-type lipase, is present in adrenal and ovary tissues. This enzyme is thought to originate from the liver and to be identical to hepatic lipase. We determined the functional molecular mass of hepatic lipase in rat liver, adrenal gland and ovary by radiation inactivation, a method for determining the functional size of a protein without the need of prior purification. Samples were exposed to ionizing radiation at -135 degrees C. Hepatic lipase activity in liver homogenate showed a single exponential decay. The functional molecular mass was calculated to be 63 +/- 10 kDa. Hepatic lipase activity in adrenal homogenate was found to have a functional molecular mass of 117 +/- 16 kDa. The functional molecular masses of the lipases partially purified from rat liver perfusate, adrenal homogenate or ovarian homogenate showed the same pattern, a target mass for the liver enzyme of 56 +/- 6 kDa and a target mass of 117 +/- 14 kDa for the enzyme from adrenal gland or ovary. In Western blot analysis the mass of the structural units of hepatic lipase in liver was 57 kDa and in adrenal and ovary tissue 51 kDa. We conclude that the functional unit of hepatic lipase in the liver is a monomer. The enzyme in adrenal gland and ovary is different from the liver and the functional unit may be a dimer.

Adrenal Glands↗