Universität zu Köln

Dias, Irundika H. K., Milic, Ivana ORCID: 0000-0001-7531-7561, Lip, Gregory Y. H., Devitt, Andrew ORCID: 0000-0002-4651-6761, Polidori, M. Cristina and Griffiths, Helen R. (2018). Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia. Redox Biol., 16. S. 139 - 146. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 2213-2317

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Abstract

Oxysterols (OHC) are biologically active cholesterol metabolites circulating in plasma that may be formed enzymatically (e.g. 24S-OHC, 25-OHC and 27-OHC) or by autoxidative mechanisms (e.g. 7-ketocholesterol, 7 beta-OHC and 25-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% and 82% and sensitivities between 5 and 135 pg/ml. 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 > 6.5 mM and ten were healthy with normal plasma cholesterol (< 6.5 mM). Simvastatin (40 mg/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 similar to 35% (p < 0.05) at the end of three months. Oxysterols generated by autoxidation (but not enzymatically) were elevated up to 45 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 within the normal range.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dias, Irundika H. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Milic, Ivana UNSPECIFIED orcid.org/0000-0001-7531-7561 UNSPECIFIED Lip, Gregory Y. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Devitt, Andrew UNSPECIFIED orcid.org/0000-0002-4651-6761 UNSPECIFIED Polidori, M. Cristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Griffiths, Helen R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-183780
DOI:	10.1016/j.redox.2018.02.014
Journal or Publication Title:	Redox Biol.
Volume:	16
Page Range:	S. 139 - 146
Date:	2018
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	2213-2317
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; CHOLESTEROL PRECURSORS; MASS-SPECTROMETRY; LDL-LIPIDS; DEMENTIA; PLASMA; STATINS; 24S-HYDROXYCHOLESTEROL; ATHEROSCLEROSIS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18378