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Title: Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: Effects of rosuvastatin
Authors: 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
Jean Mayer USDA Human Nutrition Research Center on Aging
University of Western Australia
KineMed, Inc.
Atlanta VA Medical Center
Emory University School of Medicine
Mahidol University
Pliant Therapeutics
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2017
Citation: Journal of Lipid Research. Vol.58, No.7 (2017), 1315-1324
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
ISSN: 15397262
Appears in Collections:Scopus 2016-2017

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