1. Simvastatin reduces circulating oxysterol levels in men with hypercholesterolaemia
- Author
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Irundika H.K. Dias, Gregory Y.H. Lip, M. Cristina Polidori, Ivana Milic, Helen R. Griffiths, and Andrew Devitt
- Subjects
0301 basic medicine ,Male ,Simvastatin ,Clinical Biochemistry ,SE, Standard error ,Biochemistry ,24S-OHC, 24S-hydroxycholesterol ,chemistry.chemical_compound ,0302 clinical medicine ,Tandem Mass Spectrometry ,CE, Collision Energy ,polycyclic compounds ,Medicine ,GC, Gas chromatography ,SD, Standard deviation ,SPE, Solid phase extraction ,lcsh:QH301-705.5 ,lcsh:R5-920 ,Autoxidation ,MRM, Multiple reaction monitoring method ,Oxysterols ,Middle Aged ,7-KC, 7-ketocholesterol ,3. Good health ,Cholesterol ,lipids (amino acids, peptides, and proteins) ,AD, Alzheimer's disease ,medicine.symptom ,ApoE, Apolipoprotein E ,lcsh:Medicine (General) ,LC-MS/MS, Liquid Chromatography Mass spectrometry ,medicine.drug ,Research Paper ,Adult ,medicine.medical_specialty ,Statin ,Oxysterol ,DP, Declustering potential ,medicine.drug_class ,Hypercholesterolemia ,Hydroxycholesterol ,27-OHC, 27-hydroxycholesterol ,Asymptomatic ,Vascular disease ,03 medical and health sciences ,ELISA, Enzyme linked Immunosorbent assay ,Internal medicine ,Humans ,LLOQ, lower limits of quantification ,CV, Coefficient of variation ,BHT, Butylated hydroxytoluene ,QC, Quality control ,CH25H, Cholesterol 25-hydroxylase ,Mass spectrometry ,business.industry ,CXP, exit quadrapole potential ,oxLDL, oxidised low density lipoprotein ,Organic Chemistry ,ESI, Electro spray Ionisation ,25-OHC, 25-hydroxycholesterol ,PR, Process Recovery ,030104 developmental biology ,Endocrinology ,chemistry ,lcsh:Biology (General) ,Apoptosis ,7β-OHC, 7β-hydroxycholesterol ,Dementia ,business ,030217 neurology & neurosurgery ,Lipoprotein ,Chromatography, Liquid - 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, 7β-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 (
- Published
- 2018