Publication: Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: Effects of rosuvastatin
Issued Date
2017-01-01
Resource Type
ISSN
15397262
00222275
00222275
Other identifier(s)
2-s2.0-85021725452
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Lipid Research. Vol.58, No.7 (2017), 1315-1324
Suggested Citation
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 Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: Effects of rosuvastatin. Journal of Lipid Research. Vol.58, No.7 (2017), 1315-1324. doi:10.1194/jlr.M073882 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42071
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: Effects of rosuvastatin
Abstract
Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc. 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.-Thongtang, N., M. R. Diffenderfer, E. M. M. Ooi, P. H. R. Barrett, S. M. Turner, N.-A. Le, W. V. Brown, and E. J. Schaefer. Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: effects of rosuvastatin. J. Lipid Res. 2017. 58: 1315-1324