Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients

Croyal, Mikaël; Ouguerram, Khadija; Passard, Maxime; Ferchaud‐Roucher, Véronique; Chétiveaux, Maud; Billon-Crossouard, Stéphanie; Gouville, Anne-Charlotte de; Lambert, Gilles; Krempf, Michel; Nobécourt, Estelle

doi:10.1161/atvbaha.115.305835

Cited by 51 publications

(46 citation statements)

References 36 publications

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“…This is not the case for ApoE and ApoC-III ( 20 ). The accurate detection of isoforms could be assessed by LC/MS/MS ( 10,12 ), but this is a complex analysis. We have assumed that these polymorphic variations did not signifi cantly alter the molecular masses of the targeted Apos.…”

Section: Discussionmentioning

confidence: 99%

“…From the conventional GC/MS method for ApoA-II, ApoC-II, ApoC-III, and ApoE, the comparison of our kinetic data with already published works supported the effi ciency of the LC/MS/MS method. Finally, we could easily add the kinetic analysis for Apo(a) that we have reported previously ( 12 ) to this multiplexed LC/MS/MS analysis. Along with others, we have recently shown that LC/MS/MS can also be used to quantify plasma proteins and assess protein sequence modifi cations, such as polymorphic size ( 6,(10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we could easily add the kinetic analysis for Apo(a) that we have reported previously ( 12 ) to this multiplexed LC/MS/MS analysis. Along with others, we have recently shown that LC/MS/MS can also be used to quantify plasma proteins and assess protein sequence modifi cations, such as polymorphic size ( 6,(10)(11)(12). In this study, we have focused on the concentrations and the tracer enrichments of six major human Apos, measured using a simple and fast protocol.…”

Section: Discussionmentioning

confidence: 99%

“…Chromatographic peaks having signal-to-noise ratios below the limit of quantifi cation of 10:1 were excluded and samples were reanalyzed using higher sample volumes before the concentration step (400 l). Apo concentrations were calculated using calibration curves plotted from standard solutions, as described previously ( 12 ). The…”

Section: Data Managementmentioning

confidence: 99%

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Multiplexed peptide analysis for kinetic measurements of major human apolipoproteins by LC/MS/MS

Croyal

Fall

Ferchaud‐Roucher

et al. 2016

Journal of Lipid Research

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those of the entire lipoprotein metabolism ( 1, 3 ). The incorporation of a labeled amino acid into the protein during its synthesis is subsequently measured over time and analyzed with a compartmental model to obtain the kinetic data ( 4, 5 ). The reference method to measure tracer enrichments involves isolation of the Apos by gel electrophoresis followed by acid hydrolysis to obtain unlabeled and labeled amino acids. Then, the amino acids are derivatized for GC/ MS analysis ( 3 ). These approaches are limited to one or a small number of relatively abundant Apos and remain a timeconsuming process. Kinetic studies are therefore mainly focused on the most abundant structural Apos (ApoA-I and ApoB100) and less on others, although they have a central role in lipid metabolism (ApoC-II, ApoC-III and ApoE) ( 6 ).The combination of proteomic tools, such as enzymatic proteolysis and liquid LC/MS/MS, has appeared recently to be a powerful tool to study plasma proteins ( 7-11 ). Although promising, one analytical challenge is to use this method in a single run analysis for the determination of concentrations and tracer enrichments of a signifi cant set of plasma proteins with large differences in molecular mass or abundances ( 6, 11 ).We recently published an LC/MS/MS method to simultaneously measure the concentration, tracer enrichment, and average size of Apo(a) ( 9, 12 ). In the present study, we aimed to describe the development and the validation of a multiplexed LC/MS/MS method, performing in a single run the enrichment measurements and the quantifi cation of six major human Apos (ApoA-I, ApoA-II, ApoB100, ApoC-II, ApoC-III, and ApoE) in plasma samples obtained from a stable isotope kinetic study in humans. Lipoprotein kinetic studies using radioactive or stable isotope tracers have been performed for years in humans to gain a better understanding of the mechanisms involved in lipid metabolism disturbances and related diseases ( 1, 2 ). Endogenous labeling with an amino acid tracer of Apo, a main component of lipoproteins, is commonly used, assuming the kinetics of Apos represent a good estimate of This work was supported by the Biogenouest CORSAIRE core facility.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Data Managementmentioning

confidence: 99%

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Multiplexed peptide analysis for kinetic measurements of major human apolipoproteins by LC/MS/MS

Croyal

Fall

Ferchaud‐Roucher

et al. 2016

Journal of Lipid Research

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“…Никотиновая кислота снижает уровень общего холе-стерина (ОХС), холестерина ЛНП (ХС ЛНП), тригли-церидов (ТГ) и увеличивает концентрацию холесте-рина липопротеинов высокой плотности (ХС ЛВП) [3]. По данным Croyal M. препараты НК способны достоверно снижать скорость продукции апо(а) [4]. По нашим данным, прием препарата НК замедлен-ного высвобождения (НКЗВ) у больных ИБС с гипер-липопротеидемией(а) приводит к достоверному сни-жению концентрации Лп(а) на 23% и стабилизации атеросклероза сонных артерий [5].…”

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INFLUENCE OF NICOTINIC ACID ON SUBFRACTIONAL SPECTRUM OF LOW, INTERMEDIATE AND HIGH DENSITY LIPOPROTEINS IN PATIENTS WITH HYPERLIPOPROTEINEMIA(а)

Utkina¹,

Afanas'eva²,

Артемьева³

et al. 2017

Russ J Cardiol

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Цель. Изучить влияние никотиновой кислоты (НК) на подфракционный спектр про-и анти-атерогенных липопротеидов у пациентов с гиперлипопротеи-демией(а). Материал и методы. В исследование были включены 78 пациентов с уров-нем Лп(а) более 20 мг/дл, получавшие либо комбинированную терапию НК и статинами (n=43), либо монотерапию статинами (n=13), либо монотерапию препаратом НК (n=22). Показатели липидного спектра анализировали набо-рами "Biocon/Analyticon" (Германия), количественное содержание подфрак-ций липопротеидов определяли с помощью системы Липопринт ® (Quantimetrix, INFLUENCE OF NICOTINIC ACID ON SUBFRACTIONAL SPECTRUM OF LOW, INTERMEDIATE AND HIGH DENSITY LIPOPROTEINS IN PATIENTS WITH HYPERLIPOPROTEINEMIA(а)Utkina E. A., Afanasieva O. I., Artemyeva N. V., Ezhov M. V., Pokrovsky S. N.Aim. To evaluate the influence of nicotinic acid (NA) on subfractional spectrum of pro-and antiatherogenic lipoproteides in hyperlipoproteidemia (a) patients. Material and methods. Totally, 78 patients included, with Lp(a) level more than 20 mg/dL, taking either combinational statin and NA therapy (n=43), or on monotherapy by statins (n=13), or monotherapy by NA (n=22). Lipid profile parameters were analyzed with the assays "Biocon/Analyticon" (Germany), quantitative subfractional contents were assessed with the system Lipoprint ® (Quantimetrix, USA), Lp(a)concentriation -with immune enzyme assay.Results. In combinational therapy and monotherapy groups of NA the baseline Lp(a) levels were 98,0±44,8 and 71,3±21,8 mg/dL, respectively, р<0,0001; total cholesterol (TC) 4,6±0,9 and 5,8±1,2 mM/L, р<0,0001 and low density lipoproteides cholesterol (LDL-C) 2,7±0,8 and 3,6±1,2 mM/L, р<0,05. Patients from the statins monotherapy and NA groups had significant differences by TC (4,6±1,1 and 5,8±1,2, р<0,05) and LDL-C (2,6±0,9 and 3,6±1,2, р<0,0001). In NA responders, the decrease of Lp(a) was 38%, p<0,05, in combination therapy group, and 32%, p<0,01, in monotherapy by NA group. In statin monotherapy group the Lp(a) level did not decrease. The differences were found, in the parameters of lipid profile and lipoproteides (LP) subfractions depending on the type of treatment used. In the general group of combination therapy there was significant decrease of TC, TG, LDL-C and very low density lipoproteides, and there was decline of the levels of antiatherogenic subfractions of high density lipoproteides (HDL). In monotherapy by NA group there was significant decrease of atherogenic small LDL (sLDL) from 6,9±6,7 to 3,9±4,1 mg/dL, р=0,012, and there was increase of antiatherogenic HDL subfractions. In patients on monotherapy by statins, the LP subfractions profile did not differ significantly. Conclusion. The decrease of Lp(a), atherogenic sLDL and potentially atherogenic small HDL, increase of antiathrogenic LP subfractions makes it to conclude on complex positive influence of NA on the lipoproteid subfractional profile in patients with increased Lp(a) levels, not taking statins.

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Lp(a) Metabolism

Millar

Rader

2023

Contemporary Cardiology

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Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients

Abstract: Extended-release nicotinic acid treatment decreased Apo(a) plasma concentrations by 20%, production rates by 50%, and catabolism by 37%. ApoB100 and PCSK9 concentrations were also decreased by treatment, but no correlation was found with Apo(a) kinetic parameters.

Cited by 51 publications

References 36 publications

Multiplexed peptide analysis for kinetic measurements of major human apolipoproteins by LC/MS/MS

Multiplexed peptide analysis for kinetic measurements of major human apolipoproteins by LC/MS/MS

INFLUENCE OF NICOTINIC ACID ON SUBFRACTIONAL SPECTRUM OF LOW, INTERMEDIATE AND HIGH DENSITY LIPOPROTEINS IN PATIENTS WITH HYPERLIPOPROTEINEMIA(а)

Lp(a) Metabolism

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