371 results on '"Krempf Michel"'
Search Results
352. [Management of hypercholesterolemia: what target for LDL cholesterol?].
- Author
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Cariou B and Krempf M
- Subjects
- Cardiovascular Diseases blood, Cardiovascular Diseases prevention & control, Humans, Hypercholesterolemia blood, Hypercholesterolemia therapy, Lipid Metabolism, Cholesterol, LDL blood, Hypercholesterolemia complications
- Abstract
Low-density lipoprotein cholesterol (LDL-c) concentration is an independent cardiovascular risk factor, which mostly contributes to the development and progression of atherosclerosis. Results of randomized clinical trial with statins demonstrate that the optimal LDL-c target is < 70 mg/dL. The physiological range of LDL-c in hunter-gatherers and wild mammals, who do not develop atherosclerosis, is 0.5 to 0.7 g/L. No major safety concern was found in human with genetically-related low levels of LDL-c. A moderate increase in haemorrhagic stroke and diabetes was found in some trials with statins. Guidelines recommend to modulate the LDL-c target according to the level of the total cardiovascular risk.
- Published
- 2011
353. [Radiotherapy and atherosclerosis: current data and issues].
- Author
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Gaugler MH, Drouet F, and Krempf M
- Subjects
- Atherosclerosis prevention & control, Cardiovascular Diseases prevention & control, Follow-Up Studies, Humans, Radionuclide Imaging, Radiotherapy statistics & numerical data, Risk Assessment, Atherosclerosis diagnostic imaging, Cardiovascular Diseases diagnostic imaging, Neoplasms radiotherapy, Radiotherapy adverse effects
- Abstract
The continuous optimization of cancer treatment with radiotherapy raises the problem of long-term issue of patients treated and cured by ionizing radiation, with the possible occurrence of second cancers or nonmalignant complications. Among these, cardiovascular diseases are prevalent and may affect up to 40 % of patients depending on the location of the irradiation. Recent epidemiological studies show that this problem is underestimated and with no real prospective studies. The management of these patients with vascular risk, or with very high vascular risk for those with pre-existing traditional cardiovascular risk factors, remains to be determined. The pathophysiological mechanisms of radiation-induced atherosclerosis have not yet been clarified. Many efforts are still needed to identify patients at risk and to find or to propose an appropriate treatment. Prolonged vascular follow-up of patients after their radiotherapy should now be integrated into patterns of care, especially because the setting up of sophisticated technical platforms of radiotherapy do not necessarily solve the issue of cardiovascular risk after treatment. double dagger.
- Published
- 2010
- Full Text
- View/download PDF
354. High protein intake reduces intrahepatocellular lipid deposition in humans.
- Author
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Bortolotti M, Kreis R, Debard C, Cariou B, Faeh D, Chetiveaux M, Ith M, Vermathen P, Stefanoni N, Lê KA, Schneiter P, Krempf M, Vidal H, Boesch C, and Tappy L
- Subjects
- 3-Hydroxybutyric Acid blood, Adult, Bile Acids and Salts blood, Cross-Over Studies, Dietary Fats pharmacology, Dietary Proteins administration & dosage, Energy Intake, Fatty Acids, Nonesterified blood, Humans, Insulin Resistance, Leptin blood, Male, Sterol Regulatory Element Binding Protein 1 metabolism, Tissue Plasminogen Activator blood, Young Adult, Dietary Proteins pharmacology, Lipid Metabolism genetics, Liver metabolism
- Abstract
Background: High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown., Objective: The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men., Design: Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens., Results: The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14)., Conclusions: Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.
- Published
- 2009
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355. Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect.
- Author
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Ouguerram K, Zair Y, Billon S, Chétiveaux M, Brunet-François C, Ngohou-Bach K, Allavena C, Reliquet V, Milpied B, Magot T, Raffi F, and Krempf M
- Subjects
- Adult, Apolipoprotein C-III blood, Blood Glucose metabolism, Humans, Insulin blood, Kinetics, Lipids blood, Male, Middle Aged, Models, Molecular, Antiretroviral Therapy, Highly Active, Apolipoprotein B-100 metabolism, HIV Infections metabolism, HIV-Associated Lipodystrophy Syndrome metabolism, Hyperlipidemias metabolism, Insulin Resistance physiology, Lipoproteins metabolism
- Abstract
The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment.
- Published
- 2008
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356. Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia.
- Author
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Hansel B, Nicolle C, Lalanne F, Tondu F, Lassel T, Donazzolo Y, Ferrières J, Krempf M, Schlienger JL, Verges B, Chapman MJ, and Bruckert E
- Subjects
- Animals, C-Reactive Protein metabolism, Carotenoids blood, Cholesterol analogs & derivatives, Cholesterol blood, Cholesterol pharmacology, Cholesterol, HDL blood, Cholesterol, LDL blood, Double-Blind Method, Female, Fermentation, Humans, Hypercholesterolemia blood, Male, Middle Aged, Patient Compliance, Phytosterols blood, Sitosterols blood, Sitosterols pharmacology, Treatment Outcome, Triglycerides blood, Hypercholesterolemia drug therapy, Lipids blood, Milk chemistry, Oxidative Stress drug effects, Phytosterols pharmacology
- Abstract
Background: Plant sterol (PS)-enriched foods have been shown to reduce plasma LDL-cholesterol concentrations. In most studies, however, PSs were incorporated into food products of high fat content., Objective: We examined the effect of daily consumption of PS-supplemented low-fat fermented milk (FM) on the plasma lipid profile and on systemic oxidative stress in hypercholesterolemic subjects., Design: Hypercholesterolemic subjects (LDL-cholesterol concentrations >or=130 and
- Published
- 2007
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357. [Specifics of diabetic nephropathy, viewpoint in diabetology: trends of diabetic nephropathy in diabetes].
- Author
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Krempf M
- Subjects
- Albuminuria etiology, Anemia etiology, Cardiovascular Diseases epidemiology, Denmark epidemiology, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 physiopathology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies etiology, Diabetic Nephropathies physiopathology, Global Health, Humans, Hypertension etiology, Male, Prognosis, Risk Factors, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 2 epidemiology, Diabetic Nephropathies epidemiology
- Abstract
The evolution of diabetic nephropathy has been studied by Peter Rossing on a cohort of diabetic patients followed at the Steno hospital of Copenhagen during more than 20 years. In the diabetics of type 1, existence of albuminuria at the upper threshold of the normal range, male gender, high blood pressure and poor glycemic control with a very high HbAlc are the main predictive factors of nephropathy evolution. In this population, nephropathy clearly increases the risks of mortality and cardiovascular morbidity. However, the comparison with older studies showed that better control of glycemia, blood pressure and cholesterol, reduction of tobacco consumption and improvement of proteinuria due to antihypertensive treatments, were able to sharply decrease mortality and cardiovascular morbidity with a relative risk reduction of 60%. In type 2 diabetics, besides factors observed in type 1 diabetic patients, the presence of anemia is a predictive criterion of nephropathy progression. In these patients, prevention keys lie not only in the control of glycemia and blood pressure as in type 1 diabetics, but also in that of anemia.
- Published
- 2006
358. [Diet prescription].
- Author
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Krempf M
- Subjects
- Humans, Nutrition Assessment, Nutritional Status, Diet Therapy
- Published
- 2005
359. [PCSK9: a new gene involved in familial hypercholesteremia].
- Author
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Lambert G, Costet P, Krempf M, and Lalanne F
- Subjects
- Humans, Liver metabolism, Proprotein Convertase 9, Proprotein Convertases, Receptors, LDL biosynthesis, Serine Endopeptidases physiology, Hyperlipoproteinemia Type II genetics, Serine Endopeptidases genetics
- Published
- 2004
- Full Text
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360. Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9.
- Author
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Ouguerram K, Chetiveaux M, Zair Y, Costet P, Abifadel M, Varret M, Boileau C, Magot T, and Krempf M
- Subjects
- Adult, Amino Acid Substitution, Apolipoprotein B-100, Cholesterol Esters metabolism, Female, Genes, Dominant, Humans, Hyperlipoproteinemia Type II metabolism, Lipid Metabolism, Lipoproteins metabolism, Lipoproteins, IDL, Lipoproteins, LDL metabolism, Lipoproteins, VLDL metabolism, Liver metabolism, Male, Middle Aged, Proprotein Convertase 9, Proprotein Convertases, Serine Endopeptidases chemistry, Serine Endopeptidases physiology, Apolipoproteins B biosynthesis, Hyperlipoproteinemia Type II genetics, Mutation, Missense, Point Mutation, Serine Endopeptidases genetics
- Abstract
Objective: We have reported further heterogeneity in familial autosomal-dominant hypercholesterolemia (FH) related to mutation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene previously named neural apoptosis regulated convertase 1 (Narc-1). Our aim was to define the metabolic bases of this new form of hypercholesterolemia., Methods and Results: In vivo kinetics of apolipoprotein B100-containing lipoproteins using a 14-hour primed constant infusion of [2H3] leucine was conducted in 2 subjects carrying the mutation S127R in PCSK9, controls subjects, and FH subjects with known mutations on the low-density lipoprotein (LDL) receptor gene (LDL-R). Apo B100 production, catabolism, and transfer rates were estimated from very LDL (VLDL), intermediate-density lipoprotein (IDL), and LDL tracer enrichments by compartmental analysis. PCSK9 mutation dramatically increased the production rate of apolipoprotein B100 (3-fold) compared with controls or LDL-R mutated subjects, related to direct overproduction of VLDL (3-fold), IDL (3-fold), and LDL (5-fold). The 2 subjects also showed a decrease in VLDL and IDL conversion (10% to 30% of the controls). LDL fractional catabolic rate was slightly decreased (by 30%) compared with controls but still higher than LDL-R-mutated subjects., Conclusions: These results showed that the effect of the S127R mutation of PCSK9 on plasma cholesterol homeostasis is mainly related to an overproduction of apolipoprotein B100.
- Published
- 2004
- Full Text
- View/download PDF
361. Selective uptake of high density lipoproteins cholesteryl ester in the dog, a species lacking in cholesteryl ester transfer protein activity; An in vivo approach using stable isotopes.
- Author
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Ouguerram K, Nguyen P, Krempf M, Pouteau E, Briand F, Bailhache E, and Magot T
- Subjects
- Animals, Cholesterol chemistry, Cholesterol metabolism, Cholesterol Esters metabolism, Dogs, Humans, Kinetics, Lipoproteins, HDL metabolism, Mass Spectrometry, Models, Biological, Models, Chemical, Phosphatidylcholine-Sterol O-Acyltransferase metabolism, Phosphatidylcholines chemistry, Species Specificity, Time Factors, Cholesterol Esters chemistry, Lipoproteins, HDL chemistry
- Abstract
Amongst the processes involved in the reverse cholesterol transport (RCT) from organs to liver, including high density lipoproteins-apolipoprotein AI (HDL-apoAI) dependent tissue uptake and cholesteryl ester transfer protein (CETP)-mediated transfers, the selective uptake of cholesteryl ester (CE) is of increasing interest through its antiatherogenic role. The purpose of this report is to develop a simple protocol allowing study of this process in an animal model with easier quantification of CE selective uptake. The dog was chosen essentially because this animal has a low CETP activity and an appropriate size to conduce a kinetic study. Tracer kinetics were performed to estimate in vivo the contributions of the pathways involved in HDL-CE turnover in dogs. Stable isotopes, 13C-acetate and D3-leucine as labeled precursors of CE and apoAI, were infused to fasting dogs. Isotopic enrichments were monitored in plasma unesterified cholesterol and in HDL-CE and apoAI by mass spectrometry. Kinetics were analyzed using compartmental modeling. Results concerned the measurement of the activity of cholesterol esterification (0.13+/-0.032 h(-1)), rate of HDL-apoAI catabolism (0.024+/-0.012 h(-1)), HDL-CE turnover (0.062+/-0.010 h(-1)) and CE selective uptake (0.038+/-0.014 h(-1)). Our results show that CE in dogs is mainly eliminated by selective uptake of HDL-CE (60% of HDL-CE turnover), unlike in other species studied by similar methods in our laboratory. This study shows that among species used to analyze cholesterol metabolism, the dog appears to be the animal in whom HDL-CE selective uptake represents the largest part of HDL-CE turnover.
- Published
- 2004
- Full Text
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362. [Intestinal cholesterol absorption and NPC1-L1].
- Author
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Lambert G, Chetiveaux M, Sénard G, Drui D, and Krempf M
- Subjects
- Animals, Humans, Membrane Transport Proteins, Cholesterol metabolism, Intestinal Absorption physiology, Membrane Proteins physiology, Niemann-Pick Diseases, Proteins physiology
- Published
- 2004
- Full Text
- View/download PDF
363. Resistant starch modulates in vivo colonic butyrate uptake and its oxidation in rats with dextran sulfate sodium-induced colitis.
- Author
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Moreau NM, Champ MM, Goupry SM, Le Bizec BJ, Krempf M, Nguyen PG, Dumon HJ, and Martin LJ
- Subjects
- Acute Disease, Animals, Carbon Dioxide blood, Carbon Isotopes, Cecum metabolism, Chronic Disease, Colitis metabolism, Digestion physiology, Drinking Behavior, Feeding Behavior, Intestinal Mucosa metabolism, Isotope Labeling methods, Ketone Bodies metabolism, Male, Rats, Rats, Sprague-Dawley, Weight Gain physiology, Butyrates metabolism, Colitis chemically induced, Colon metabolism, Dextran Sulfate pharmacology, Gastrointestinal Transit physiology, Starch pharmacology
- Abstract
We previously demonstrated improvements of colonic lesions due to dextran sulfate sodium (DSS) in rats after 7 d of supplementation with resistant starch (RS) type 3, a substrate yielding high levels of butyrate (C(4)), a colonic cell fuel source. In the present study, we hypothesized that if inflammation is related to decreased C(4) utilization by the colonic mucosa, RS supplementation should restore C(4) use simultaneously with an increase in the amount of C(4) present in the digestive tract. Hence, we compared, in vivo, the cecocolonic uptake of C(4) and its oxidation into CO(2) and ketone bodies in control and DSS-treated rats fed a fiber-free basal diet (BD) or a RS-supplemented diet. Sprague-Dawley rats (n = 60) were used. DSS treatment was performed to induce acute colitis and then to maintain chronic colitis. After cecal infusion of [1-(13)C]-C(4) (20 micro mol in 1 h), concentrations and (13)C-enrichment of C(4), ketone bodies, and CO(2) were quantified in the abdominal aorta and portal vein. Portal blood flow was recorded. During acute colitis, (13)C(4) uptake and (13)CO(2) production were lower in DSS rats than in controls. During chronic colitis, DSS rats did not differ from controls. After 7 d of chronic colitis, RS-DSS rats exhibited the same C(4) uptake as BD-DSS rats in spite of higher C(4) cecocolonic disposal. After 14 d, C(4) uptake was higher in RS-DSS than in BD-DSS rats. Thus, the increased utilization of C(4) by the mucosa is subsequent to evidence of healing and appears to be a consequence rather than a cause of this RS healing effect.
- Published
- 2004
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364. Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes.
- Author
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Ouguerram K, Magot T, Zaïr Y, Marchini JS, Charbonnel B, Laouenan H, and Krempf M
- Subjects
- Adult, Aged, Apolipoprotein B-100, Apolipoproteins B drug effects, Atorvastatin, Female, Humans, Kinetics, Lipid Metabolism, Lipoproteins, LDL metabolism, Lipoproteins, VLDL metabolism, Male, Middle Aged, Anticholesteremic Agents pharmacology, Apolipoproteins B metabolism, Diabetes Mellitus, Type 2 metabolism, Heptanoic Acids pharmacology, Lipoproteins metabolism, Pyrroles pharmacology
- Abstract
Seven hypertriglyceridemic patients with type-2 diabetes were treated with atorvastatin (40 mg/day) for 2 months. Kinetics of apolipoprotein B100 (apoB100)-containing lipoproteins were determined before and after atorvastatin treatment and compared with data obtained in five normolipidemic volunteers. ApoB100 metabolism was studied using stable isotopes and multicompartmental modeling. Compared with normolipidemic obese subjects, type-2 diabetic patients had a higher apoB100 concentration in very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL) (P < 0.005). Kinetic analysis showed an increase in the total apoB100 production rate (P < 0.005) related to VLDL apoB100 overproduction (P < 0.005). Patients were also characterized by a lower fractional catabolic rate (FCR) in VLDL (not significant) or IDL (P < 0.005) mainly related to a decrease in VLDL and IDL delipidation rate (P < 0.005). Catabolism of LDL was also lower in diabetic patients (P < 0.05). Atorvastatin treatment significantly decreased plasma triglycerides (P < 0.05), total and LDL cholesterol (P < 0.05), apoB100 in LDL, IDL, and VLDL (P < 0.05). Treatment significantly decreased total apoB100 production rate (P < 0.05), but only for VLDL (P < 0.05). Treatment normalized FCR in IDL and LDL (P < 0.05). We concluded that atorvastatin improved lipid abnormalities in type-2 diabetic patients not only by increasing the clearance of apoB100-containing lipoproteins but also by decreasing VLDL production.
- Published
- 2003
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365. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.
- Author
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Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, and Boileau C
- Subjects
- Amino Acid Substitution, Chromosomes, Human, Pair 1 genetics, Female, Genes, Dominant, Genetic Linkage, Humans, Hyperlipoproteinemia Type II enzymology, Liver enzymology, Male, Pedigree, Proprotein Convertase 9, Proprotein Convertases, Hyperlipoproteinemia Type II genetics, Mutation, Serine Endopeptidases genetics
- Abstract
Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.
- Published
- 2003
- Full Text
- View/download PDF
366. Lipoproteins abnormalities in obese insulin-resistant dogs.
- Author
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Bailhache E, Nguyen P, Krempf M, Siliart B, Magot T, and Ouguerram K
- Subjects
- Animals, Blood Glucose metabolism, Body Weight physiology, Chromatography, High Pressure Liquid, Diet, Dogs, Glucose Clamp Technique, Hyperinsulinism blood, Insulin blood, Lipoproteins blood, Lipoproteins, HDL blood, Lipoproteins, VLDL blood, Male, Obesity blood, Triglycerides blood, Insulin Resistance physiology, Lipoproteins metabolism, Obesity metabolism
- Abstract
Many studies have shown that obesity and low insulin sensitivity are associated with lipoprotein abnormalities, which are risk factors for coronary heart disease. The effects of insulin resistance on lipoprotein metabolism were investigated in hyperenergetic-fed beagle dogs, a new model of insulin resistance. Insulin resistance was assessed by the 3-hour euglycemic-hyperinsulinemic glucose clamp technique. Lipoproteins were separated by fast-protein liquid chromatography (FPLC) and lipid composition of the different lipoproteins was determined by enzymatic methods. Hyperenergetic diet was associated with a 43% +/- 5% increase in dog body weight and a reduction in insulin-mediated glucose uptake (28 +/- 3 to 16 +/- 1 mg. kg(-1). min(-1), P <.05). Low insulin sensitivity associated with obesity was related to an increase in plasma triglyceride (TG) through an increase in very-low-density lipoprotein (VLDL)-TG (0.071 +/- 0.020 v 0.382 +/- 0.242 mmol/L, P <.05) and high-density lipoprotein (HDL)-TG (0.025 +/- 0.012 v 0.242 +/- 0.143 mmol/L, P <.05). Other lipid abnormalities common in insulin resistant humans were also found: lower plasma HDL-cholesterol (4.690 +/- 0.151 v 3.937 +/- 0.141 mmol/L, P <.05) and higher plasma nonesterified fatty acids (NEFA) (0.974 +/- 0.094 v 1.590 +/- 0.127 mmol/L, P <.05) levels. These data show that this model of the insulin-resistant obese dog could be useful in studying insulin resistance-associated dyslipidemia., (Copyright 2003 Elsevier Inc. All rights reserved.)
- Published
- 2003
- Full Text
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367. Production rates and metabolism of short-chain fatty acids in the colon and whole body using stable isotopes.
- Author
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Pouteau E, Nguyen P, Ballèvre O, and Krempf M
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- Acetates metabolism, Acetates pharmacokinetics, Animals, Carbon Isotopes, Fatty Acids, Volatile metabolism, Humans, Intestinal Absorption, Rats, Colon metabolism, Fatty Acids, Volatile pharmacokinetics
- Abstract
Short-chain fatty acids (SCFA; mainly acetate, propionate and butyrate) are largely produced in non-ruminants during the colonic bacterial fermentation of non-digestible carbohydrates. These intestinal exogenous SCFA pass in part through the splanchnic bed and reach the peripheral bloodstream, mixing with the endogenous circulating SCFA. The whole-body turnover of SCFA is thus composed of an endogenous peripheral turnover and an exogenous production that depends on dietary intake of non-digestible carbohydrates. In the present work methods were developed for determining the SCFA turnover in animals and in human subjects using stable isotopes. The original studies performed to determine endogenous and exogenous metabolism of SCFA in animals and in human subjects are summarised. Using intravenous infusion of 13C-labelled SCFA the whole-body turnover of acetate, propionate and butyrate was assessed in rats in a fasted state. The endogenous turnover of acetate and its oxidation were determined in healthy human subjects in the post-absorptive state, using intravenous infusion of [1-13C]acetate. Intragastric tracer infusions were performed to evaluate the splanchnic first-pass retention of acetate in adults. Finally, an original model was developed in healthy human subjects using intravenous infusion of [1-13C]acetate to determine in vivo the true colonic acetate production after ingestion of a non-digestible disaccharide. These present studies using stable isotopes provide the basis for a novel strategy to evaluate in vivo, in human subjects, the production of SCFA in the large intestine.
- Published
- 2003
- Full Text
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368. Intronic mutations outside of Alu-repeat-rich domains of the LDL receptor gene are a cause of familial hypercholesterolemia.
- Author
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Amsellem S, Briffaut D, Carrié A, Rabès JP, Girardet JP, Fredenrich A, Moulin P, Krempf M, Reznik Y, Vialettes B, de Gennes JL, Brukert E, and Benlian P
- Subjects
- Base Sequence, DNA Primers, Exons, Humans, Hyperlipoproteinemia Type II genetics, Introns, Mutation, Receptors, LDL genetics, Repetitive Sequences, Nucleic Acid
- Abstract
Familial hypercholesterolemia (FH), a frequent monogenic condition complicated by premature cardiovascular disease, is characterized by high allelic heterogeneity at the low-density lipoprotein receptor ( LDLR) locus. Despite more than a decade of genetic testing, knowledge about intronic disease-causing mutations has remained limited because of lack of available genomic sequences. Based on the finding from bioinformatic analysis that Alu repeats represent 85% of LDLR intronic sequences outside exon-intron junctions, we designed a strategy to improve the exploration of genomic regions in the vicinity of exons in 110 FH subjects from an admixed population. In the first group of 42 patients of negative mutation carriers, as previously established by former screening strategies (denaturing gradient gel electrophoresis, DNA sequencing with former primers overlapping splice-sites, Southern Blotting), about half ( n=22) were found to be carriers of at least one heterozygous mutation. Among a second group of 68 newly recruited patients, 27% of mutation carriers ( n=37) had a splicing regulatory mutation. Overall, out of the 54 mutations identified, 13 were intronic, and 18 were novel, out of which nearly half were intronic. Two novel intronic mutations (IVS8-10G-->A within the polypyrimidine tract and IVS7+10G-->A downstream of donor site) might create potential aberrant splice sites according to neural-network computed estimation, contrary to 31 common single nucleotide variations also identified at exon-intron junctions. This new strategy of detecting the most likely disease-causing LDLR mutations outside of Alu-rich genomic regions reveals that intronic mutations may have a greater impact than previously reported on the molecular basis of FH.
- Published
- 2002
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369. The differential apoA-I enrichment of prebeta1 and alphaHDL is detectable by gel filtration separation.
- Author
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Chétiveaux M, Nazih H, Ferchaud-Roucher V, Lambert G, Zaïr Y, Masson M, Ouguerram K, Bouhours D, and Krempf M
- Subjects
- Apolipoprotein A-I isolation & purification, Humans, Kinetics, Lipoproteins, HDL classification, Ultracentrifugation, Apolipoprotein A-I blood, Chromatography, High Pressure Liquid methods, Lipoproteins, HDL blood, Lipoproteins, HDL isolation & purification
- Abstract
The aim of the study was to assess the isolation of HDL by fast protein liquid chromatography (FPLC) to perform kinetics studies of apolipoprotein (apo)A-I-HDL labelled with a stable isotope. Comparison between FPLC and ultracentrifugation has been made. ApoA-I-HDL kinetics were studied by infusion of [5.5.5-(2)H(3)]leucine for 14 h in five subjects. Using FPLC, prebeta(1) HDL and alphaHDL (HDL(2) and HDL(3)) were separated from 200 microl of plasma samples. Total HDL was isolated by sequential ultracentrifugation (HDL-UC). The tracer-to-tracee ratio was higher in prebeta(1) HDL than in total HDL-UC. The higher leucine enrichment found in total HDL-UC compared to alphaHDL suggested the existence of a mixture of apoA-I-HDL sub-classes. From this difference in enrichments, the turnover rate of total HDL-UC, usually assumed to be alphaHDL, was probably overestimated in previous studies. To our knowledge, this study is the first report which provides a convenient tool to distinguish enrichments of apoA-I in prebeta(1) HDL and alphaHDL from total HDL previously used for kinetic measurements. This original and new method should help to understand the kinetics of HDL in humans and the reverse cholesterol transport dynamics.
- Published
- 2002
- Full Text
- View/download PDF
370. Quantitative measurement of lipoprotein particles containing both apolipoprotein AIV and apolipoprotein B in human plasma by a noncompetitive ELISA.
- Author
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Ferrer F, Bigot-Corbel E, N'Guyen P, Krempf M, and Bard JM
- Subjects
- Cholesterol blood, Enzyme-Linked Immunosorbent Assay, Female, Humans, Hyperlipidemias blood, Male, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Triglycerides blood, Apolipoproteins A blood, Apolipoproteins B blood
- Abstract
Background: A reliable method for plasma would be useful to investigate the role of apolipoprotein (apo) AIV when associated with apo B-containing or triglyceride-rich lipoproteins., Method: We used a sandwich ELISA to quantify lipoprotein B:AIV particles (Lp B:AIVf; lipoproteins containing at least apo B and apo AIV) in plasma. The method used microtiter plates coated with purified anti-apo B immunoglobulins that selectively retained apo B-containing particles. Lipoproteins containing both apo B and apo AIV were distinguished from those containing only apo B by use of a peroxidase-labeled anti-apo AIV antibody. These subspecies were revealed by ABTS reagent and further quantified by spectrophotometry. Results were expressed in mg/L apo AIV associated with apo B. This method was applied to samples with different cholesterol and triglyceride concentrations., Results: The developed sandwich ELISA method identified and quantified Lp B:AIVf in plasma samples. Within- and between-run CVs were approximately 10%, and analytical recoveries were 95-107%. Results were not significantly influenced by addition of triglycerides or by storage at -20 degrees C (up to 9 months). Under these conditions, plasma Lp B:AIVf concentrations were statistically higher in hypercholesterolemic and mixed hyperlipidemic individuals (53 +/- 13 mg/L; P <0.001 and 70 +/- 18 mg/L; P <0.001, respectively) than in normolipidemic individuals (43 +/- 12 mg/L). Lp B:AIVf concentration appeared to be well correlated with total cholesterol, triglycerides, LDL-cholesterol, and apo B. These results were in contrast to total apo AIV, which was not different between dyslipidemic and normolipidemic individuals., Conclusions: The developed ELISA method for Lp B:AIVf in plasma combines specificity, reliability, and speed. The increase in Lp B:AIVf concentrations in various dyslipidemic states, together with a lack of change in total apo AIV concentrations, suggests a redistribution of apo AIV toward apo B-containing lipoproteins when these lipoproteins accumulate.
- Published
- 2002
371. Rate of carbon dioxide production and energy expenditure in fed and food-deprived adult dogs determined by indirect calorimetry and isotopic methods.
- Author
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Pouteau EB, Mariot SM, Martin LJ, Dumon HJ, Mabon FJ, Krempf MA, Robins RJ, Darmaun DH, Naulet NA, and Nguyen PG
- Subjects
- Animals, Carbon Isotopes, Deuterium, Female, Male, Oxygen Isotopes, Calorimetry, Indirect veterinary, Carbon Dioxide metabolism, Dogs metabolism, Energy Metabolism physiology, Food Deprivation physiology, Isotopes
- Abstract
Objective: To evaluate energy expenditure (EE) in dogs by estimating rate of CO2 production (rCO2)., Animals: 15 Beagles., Procedure: Food was withheld for 24 hours, and all dogs received an IV infusion of 13C sodium bicarbonate for 8 hours. Breath samples were collected before infusion and at 30-minute intervals from 4 to 8 hours, and 13C enrichment in breath CO2 was measured, using gas chromatography-isotopic ratio mass spectrometry. Food was withheld from 6 dogs, and rCO2 and O2 consumption were measured, using a conventional indirect calorimeter. The CO2 production and O2 consumption were measured by use of indirect calorimetry in 6 other fed dogs that were injected with 2H2O and H2(18)O. Blood samples were collected before tracer injection, 4 hours later, and on days 4, 7, and 11. Deuterium and 18O enrichments in plasma water were determined., Results: Mean rCO2 measured by indirect calorimetry was 516 +/- 34 and 410 +/- 16 micromol/kg(0.75)/min in 6 fed and 6 food-deprived dogs, respectively. The rCO2 calculated from 13C-bicarbonate dilution was 482 +/- 30 micromol/kg(0.75)/min. Mean rCO2 determined by use of the double-labeled water method was 1,036 +/- 46 mmol/kg(0.75)/d. Mean energy expenditure calculated from rCO2 determined by infusion of 13C bicarbonate, indirect calorimetry in fed and food-deprived dogs, and infusion of double-labeled water was 386 +/- 39, 379 +/- 25, 338 +/- 14, and 552 +/- 25 kJ/kg(0.75)/d, respectively., Conclusions and Clinical Relevance: Energy expenditure calculated by indirect calorimetry in unfed dogs can be considered representative of basal metabolic rate.
- Published
- 2002
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