Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome

Theodore Wai Ng, Esther Ooi, Gerald Watts, Dick Chan, J.M. Weir, P.J. Meikle, Hugh Barrett

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15 Citations (Scopus)

Abstract

Copyright © 2014 by the Endocrine Society. Context: Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes. Objective: The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome. Methods: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry. Results: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P <.001 unless stated otherwise) lowered plasma cholesterol (-34% and -42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33%and -37%), sphingomyelin (-27% and-31%), monohexosylceramide (-40% and-47%), dihexosylceramide (-31% and-34%), and trihexosylceramide (-29% and-31%), and GM3 gangliosides (-29% and-26%), lysophosphatidylcholine (-32% and-37%), alkylphosphatidylcholine (-19% and-19%), phosphatidylcholine (-17% and-19%), alkenylphosphatidylcholine (plasmalogen) (-20% and-22%), alkylphosphatidylethanolamine (-20%, P-.008 and-24%, P =.02), alkenylphosphatidylethanolamine (plasmalogen) (-24%, P =.003 and-23%, P =.007), phosphatidylglycerol (-24%, P =.07,-31%, P =.046), and phosphatidylinositol (-34% and-40%). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine (plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration. Conclusions: Rosuvastatin dose-dependently lowers plasma sphingolipids and phospholipids, independent of low-density lipoprotein lowering, in men with the metabolic syndrome.
Original languageEnglish
Pages (from-to)E2335-E2340
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number11
DOIs
Publication statusPublished - 2014

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Sphingolipids
Allura Red AC Dye
Plasmas
Plasmalogens
Phosphatidylcholines
Lysophosphatidylcholines
Phosphatidylinositols
Trihexosylceramides
Phospholipids
Cholesterol
Placebos
G(M3) Ganglioside
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cardiovascular Agents
Electrospray ionization
Phosphatidylglycerols
Sphingomyelins
Electrospray Ionization Mass Spectrometry
Ceramides
Phosphatidylserines

Cite this

@article{899e4e1315c145f38c6e690ed59ba51c,
title = "Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome",
abstract = "Copyright {\circledC} 2014 by the Endocrine Society. Context: Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes. Objective: The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome. Methods: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry. Results: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P <.001 unless stated otherwise) lowered plasma cholesterol (-34{\%} and -42{\%} [{\%} change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49{\%} and -57{\%}) and triglyceride (-24{\%}, P =.03 and -42{\%}) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33{\%}and -37{\%}), sphingomyelin (-27{\%} and-31{\%}), monohexosylceramide (-40{\%} and-47{\%}), dihexosylceramide (-31{\%} and-34{\%}), and trihexosylceramide (-29{\%} and-31{\%}), and GM3 gangliosides (-29{\%} and-26{\%}), lysophosphatidylcholine (-32{\%} and-37{\%}), alkylphosphatidylcholine (-19{\%} and-19{\%}), phosphatidylcholine (-17{\%} and-19{\%}), alkenylphosphatidylcholine (plasmalogen) (-20{\%} and-22{\%}), alkylphosphatidylethanolamine (-20{\%}, P-.008 and-24{\%}, P =.02), alkenylphosphatidylethanolamine (plasmalogen) (-24{\%}, P =.003 and-23{\%}, P =.007), phosphatidylglycerol (-24{\%}, P =.07,-31{\%}, P =.046), and phosphatidylinositol (-34{\%} and-40{\%}). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine (plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration. Conclusions: Rosuvastatin dose-dependently lowers plasma sphingolipids and phospholipids, independent of low-density lipoprotein lowering, in men with the metabolic syndrome.",
author = "Ng, {Theodore Wai} and Esther Ooi and Gerald Watts and Dick Chan and J.M. Weir and P.J. Meikle and Hugh Barrett",
year = "2014",
doi = "10.1210/jc.2014-1665",
language = "English",
volume = "99",
pages = "E2335--E2340",
journal = "Journal of Endocrinology & Metabolism",
issn = "0021-972X",
publisher = "ENDOCRINE SOC",
number = "11",

}

TY - JOUR

T1 - Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome

AU - Ng, Theodore Wai

AU - Ooi, Esther

AU - Watts, Gerald

AU - Chan, Dick

AU - Weir, J.M.

AU - Meikle, P.J.

AU - Barrett, Hugh

PY - 2014

Y1 - 2014

N2 - Copyright © 2014 by the Endocrine Society. Context: Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes. Objective: The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome. Methods: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry. Results: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P <.001 unless stated otherwise) lowered plasma cholesterol (-34% and -42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33%and -37%), sphingomyelin (-27% and-31%), monohexosylceramide (-40% and-47%), dihexosylceramide (-31% and-34%), and trihexosylceramide (-29% and-31%), and GM3 gangliosides (-29% and-26%), lysophosphatidylcholine (-32% and-37%), alkylphosphatidylcholine (-19% and-19%), phosphatidylcholine (-17% and-19%), alkenylphosphatidylcholine (plasmalogen) (-20% and-22%), alkylphosphatidylethanolamine (-20%, P-.008 and-24%, P =.02), alkenylphosphatidylethanolamine (plasmalogen) (-24%, P =.003 and-23%, P =.007), phosphatidylglycerol (-24%, P =.07,-31%, P =.046), and phosphatidylinositol (-34% and-40%). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine (plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration. Conclusions: Rosuvastatin dose-dependently lowers plasma sphingolipids and phospholipids, independent of low-density lipoprotein lowering, in men with the metabolic syndrome.

AB - Copyright © 2014 by the Endocrine Society. Context: Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes. Objective: The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome. Methods: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry. Results: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P <.001 unless stated otherwise) lowered plasma cholesterol (-34% and -42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33%and -37%), sphingomyelin (-27% and-31%), monohexosylceramide (-40% and-47%), dihexosylceramide (-31% and-34%), and trihexosylceramide (-29% and-31%), and GM3 gangliosides (-29% and-26%), lysophosphatidylcholine (-32% and-37%), alkylphosphatidylcholine (-19% and-19%), phosphatidylcholine (-17% and-19%), alkenylphosphatidylcholine (plasmalogen) (-20% and-22%), alkylphosphatidylethanolamine (-20%, P-.008 and-24%, P =.02), alkenylphosphatidylethanolamine (plasmalogen) (-24%, P =.003 and-23%, P =.007), phosphatidylglycerol (-24%, P =.07,-31%, P =.046), and phosphatidylinositol (-34% and-40%). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine (plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration. Conclusions: Rosuvastatin dose-dependently lowers plasma sphingolipids and phospholipids, independent of low-density lipoprotein lowering, in men with the metabolic syndrome.

U2 - 10.1210/jc.2014-1665

DO - 10.1210/jc.2014-1665

M3 - Article

VL - 99

SP - E2335-E2340

JO - Journal of Endocrinology & Metabolism

JF - Journal of Endocrinology & Metabolism

SN - 0021-972X

IS - 11

ER -