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 language | English |
|---|---|
| Pages (from-to) | 1315-1324 |
| Number of pages | 10 |
| Journal | Journal of Lipid Research |
| Volume | 58 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2017 |
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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 journal › Article
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 -