Simvastatin reduces circulating oxysterol levels in men with hypercholesterolemia


Oxysterols (OHC) are biologically active cholesterol metabolites circulating in plasma that may be formed enzymatically (e.g. 24S-OHC, 25S-OHC and 27-OHC) or by autoxidative mechanisms (e.g. 7-ketocholesterol, 7β-OHC and 25S-OHC). Oxysterols are more soluble than cholesterol and are reported to exert inflammatory, cytoprotective and apoptotic effects according to concentration and species. Esterified oxysterols have been analysed in people with dementia and cardiovascular diseases although there is no consistent relationship between oxysterol esters and disease. However, oxysterol esters are held in lipoprotein core and may not relate to the concentration and activity of plasma free oxysterols. Methodological limitations have challenged the analysis of free oxysterols to date. We have developed a fast, sensitive and specific quantitative LC-MS/MS, multiple reaction monitoring (MRM) method to target five oxysterols in human plasma with analyte recoveries between 72-82 % and sensitivities between 5-135ng. A novel method was used to investigate the hypothesis that simvastatin may reduce the concentrations of specific plasma free oxysterols in hypercholesterolaemia. Twenty healthy male volunteers were recruited (aged 41-63 years); ten were asymptomatic with high plasma cholesterol >6.5mM and ten were healthy with normal plasma cholesterol (<6.5mM). Simvastatin (40mg/day) was prescribed to those with hypercholesterolaemia. Plasma samples were taken from both groups at baseline and after three months. Simvastatin reduced plasma cholesterol by ~35% (p<0.05) at the end of three months. Oxysterols generated by autoxidation but not enzymatically were elevated more than 100 fold in hypercholesterolaemic midlife men. Plasma oxysterols were restored to those of healthy controls after simvastatin intervention suggesting that autoxidation is either prevented by simvastatin directly or that autoxidation is less prevalent when plasma cholesterol concentrations are in the normal range.

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Divisions: College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (
Uncontrolled Keywords: hydroxycholesterol, mass spectrometry, statin, vascular disease, dementia
Publication ISSN: 2213-2317
Last Modified: 11 Apr 2024 07:12
Date Deposited: 16 Feb 2018 12:40
Full Text Link: http://europepm ... ct/med/29501047
Related URLs: https://www.sci ... 0995?via%3Dihub (Publisher URL)
PURE Output Type: Article
Published Date: 2018-06-01
Published Online Date: 2018-02-17
Accepted Date: 2018-02-15
Authors: Dias, Heraliyawala K (ORCID Profile 0000-0002-6620-8221)
Milic, Ivana (ORCID Profile 0000-0001-7531-7561)
Lip, Gregory Y.H.
Polidori, Maria Cristina
Devitt, Andrew (ORCID Profile 0000-0002-4651-6761)
Griffiths, Helen R (ORCID Profile 0000-0002-2666-2147)



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