Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: effects of rosuvastatin

Nuntakorn Thongtang, Margaret R Diffenderfer, Esther M M Ooi, P Hugh R Barrett, Scott M Turner, Ngoc-Anh Le, W Virgil Brown, Ernst J Schaefer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d= 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P< 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P< 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.

Original languageEnglish
Pages (from-to)1315-1324
Number of pages10
JournalJournal of Lipid Research
Volume58
Issue number7
DOIs
Publication statusPublished - Jul 2017

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Hyperlipidemias
Metabolism
Proteomics
Apolipoprotein B-100
Lipoproteins
Triglycerides
oxidized low density lipoprotein
Rosuvastatin Calcium
Placebos
Apolipoprotein C-III
Isotopes
Mass spectrometry
Mass Spectrometry

Cite this

Thongtang, Nuntakorn ; Diffenderfer, Margaret R ; Ooi, Esther M M ; Barrett, P Hugh R ; Turner, Scott M ; Le, Ngoc-Anh ; Brown, W Virgil ; Schaefer, Ernst J. / Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia : effects of rosuvastatin. In: Journal of Lipid Research. 2017 ; Vol. 58, No. 7. pp. 1315-1324.
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abstract = "Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d= 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45{\%}; lbLDL, +131{\%}; and sdLDL, +97{\%}), without a change in production. On placebo, 25{\%} of TRL apoB-100 was catabolized directly, 37{\%} was converted to lbLDL, and 38{\%} went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P< 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P< 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.",
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Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia : effects of rosuvastatin. / Thongtang, Nuntakorn; Diffenderfer, Margaret R; Ooi, Esther M M; Barrett, P Hugh R; Turner, Scott M; Le, Ngoc-Anh; Brown, W Virgil; Schaefer, Ernst J.

In: Journal of Lipid Research, Vol. 58, No. 7, 07.2017, p. 1315-1324.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia

T2 - effects of rosuvastatin

AU - Thongtang, Nuntakorn

AU - Diffenderfer, Margaret R

AU - Ooi, Esther M M

AU - Barrett, P Hugh R

AU - Turner, Scott M

AU - Le, Ngoc-Anh

AU - Brown, W Virgil

AU - Schaefer, Ernst J

N1 - Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

PY - 2017/7

Y1 - 2017/7

N2 - Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d= 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P< 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P< 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.

AB - Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d= 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P< 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P< 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.

KW - Cholesterol, LDL

KW - Female

KW - Humans

KW - Hyperlipidemia, Familial Combined

KW - Male

KW - Middle Aged

KW - Particle Size

KW - Proteomics

KW - Rosuvastatin Calcium

KW - Journal Article

U2 - 10.1194/jlr.M073882

DO - 10.1194/jlr.M073882

M3 - Article

VL - 58

SP - 1315

EP - 1324

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 7

ER -