Serum lipoprotein distribution, flotation rates and protein analysis

Lindgren, Frank T.; Freeman, N. K.; Ewing, A. M.; Jensen, L. C.

doi:10.1007/bf02609674

Cited by 15 publications

(1 citation statement)

References 17 publications

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“…There are several methods to assess lipoproteins. The sequential or density gradient ultracentrifugation of lipoproteins has been a standard for quantitative analysis of lipoproteins for many years [12][13][14] . Agarose or polyacrylamide gel (PAG) disc electrophoresis has also been used to qualitatively analyze the abnormalities of lipoproteins in dyslipidemic patients.…”

Section: Introductionmentioning

confidence: 99%

Distinct Differences in Lipoprotein Particle Number Evaluation between GP-HPLC and NMR: Analysis in Dyslipidemic Patients Administered a Selective PPARα Modulator, Pemafibrate

Yamashita¹,

Okazaki

Okada

et al. 2021

JAT

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We established a method to evaluate the lipid concentrations, size and particle numbers (PNs) of lipoprotein subclasses by gel permeation chromatography (GP-HPLC). Nuclear magnetic resonance (NMR) is widely used to analyze these parameters of lipoprotein subclasses, but differences of the two methods are unknown. Current study compared the PNs of each lipoprotein subclass measured by GP-HPLC and NMR, and assessed the effect of a selective PPAR modulator, pemafibrate. Methods: Lipoprotein profiles of 212 patients with dyslipidemia who participated in the phase 2 clinical trial of a selective PPAR modulator, pemafibrate, were analyzed by two methods, GP-HPLC and NMR, which were performed with LipoSEARCH (Skylight Biotech) and LipoProfile 3 (LabCorp), respectively. GP-HPLC evaluated the PNs of 18 subclasses, consisting of CM, VLDL1-5, LDL1-6, and HDL1-6. NMR evaluated the PNs of 9 subclasses, consisting of large VLDL & CM, medium VLDL, small VLDL, IDL, large LDL, small LDL, large HDL, medium HDL and small HDL. Results: Three major classes, total CM&VLDL, total LDL and total HDL were obtained by grouping of corresponding subclasses in both methods and PNs of these classes analyzed by GP-HPLC were correlated positively with those by NMR. The correlation coefficients in total CM&VLDL, total LDL and total HDL between GP-HPLC and NMR was 0.658, 0.863 and 0.798 (all p 0.0001), respectively. The PNs of total CM&VLDL, total LDL and total HDL analyzed by GP-HPLC was 249.5 51.7nM, 1,679 359 nM and 13,273 1,564 nM, respectively, while those by NMR was 124.6 41.8 nM, 1,514 386 nM and 31,161 4,839 nM, respectively. A marked difference in the PNs between the two methods was demonstrated especially in total HDL.The number of apolipoprotein (Apo) B molecule per one ApoB-containing lipoprotein particle, total CM&VLDL plus total LDL, was 1.10 0.05 by GP-HPLC, while 1.32 0.18 by NMR. The number of ApoA-I per one HDL particle was 3.40 0.17 by GP-HPLC, but only 1.46 0.15 by NMR, much less than reported previously.From the phase 2 clinical trial, randomizing 212 patients to pemafibrate 0.025-0.2 mg BID, fenofibrate 100 mg QD, or placebo groups, pemafibrate reduced the PNs of CM, large VLDL1-VLDL3 and medium VLDL4, but not small VLDL5 by GP-HPLC. It significantly decreased the PNs of smaller LDL and larger HDL particles, but increased those of larger LDL and smaller HDL particles. In contrast, NMR showed marked variations in the effect of pemafibrate on lipoprotein PNs, and no significant size-dependent changes.Conclusions: GP-HPLC evaluates the lipoprotein PNs more accurately than NMR and can be used for assessing the effects of lipid-lowering drugs on lipoprotein subclasses.

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Section: Introductionmentioning

confidence: 99%

Distinct Differences in Lipoprotein Particle Number Evaluation between GP-HPLC and NMR: Analysis in Dyslipidemic Patients Administered a Selective PPARα Modulator, Pemafibrate

Yamashita¹,

Okazaki

Okada

et al. 2021

JAT

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Flotation rates, molecular weights and hydrated densities of the low‐density lipoproteins

Lindgren

Jensen

Wills

et al. 1969

Lipids

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A method involving three computer programs is described for characterizing the major component of the Sf 0–12 low‐density lipoprotein class by its Sf rate, hydrated density and molecular weight. All necessary information is obtained from a standard low and high‐density lipoprotein ultracentrifugal analysis. Moving‐boundary flotation rates are measured in 1.061 g/ml sodium chloride and 1.200 g/ml sodium bromide solutions and are corrected to flotation at zero concentration. Hydrated densities are calculated from η Fo versus ρ plots and minimum hydrated molecular weights calculated using Stokes' frictional factor, assuming spherical molecules. Preliminary application of this procedure indicates higher Sfo rates, higher molecular weights, and lower hydrated densities in females than in males. Molecular weights and standard deviations of the principal Sf 0–12 component for non‐fasting normal adult females and males were 2.36±0.16 and 2.12±0.20 millions, respectively.

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Comparison of lipoprotein analysis by agarose gel and paper electrophoresis with analytical ultracentrifugation

Noble

Hatch

Marzimas

et al. 1969

Lipids

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A comparison has been made of human serum lipoprotein analysis by agarose gel and paper electrophoresis with a standard method of analytical ultracentrifugation. Samples were obtained from 28 patients with various disorders of lipoprotein metabolism. Correspondence was shown between the following electrophoretic and ultracentrifugal fractions: β and Sf 0–20; pre‐β and Sf 20–400; α1 and total HDL. The deviations observed with the electrophoretic methods, though sizable, were smaller than the usual clinically significant abnormalities. Semiquantitative application is there fore justified. Agarose gel electrophoresis is slightly more difficult than paper electrophoresis, but gives improved resolution of pre‐β‐ and β‐lipoproteins and better densitometric scans. Evidence was also presented that the agarose method, when used in conjuction which ultracentrifugation, may be a valuable research technique for the study of lipoprotein properties.

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Serum lipoprotein distribution, flotation rates and protein analysis

Cited by 15 publications

References 17 publications

Distinct Differences in Lipoprotein Particle Number Evaluation between GP-HPLC and NMR: Analysis in Dyslipidemic Patients Administered a Selective PPARα Modulator, Pemafibrate

Distinct Differences in Lipoprotein Particle Number Evaluation between GP-HPLC and NMR: Analysis in Dyslipidemic Patients Administered a Selective PPARα Modulator, Pemafibrate

Flotation rates, molecular weights and hydrated densities of the low‐density lipoproteins

Comparison of lipoprotein analysis by agarose gel and paper electrophoresis with analytical ultracentrifugation

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