In:
British Journal of Clinical Pharmacology, Wiley, Vol. 87, No. 11 ( 2021-11), p. 4252-4261
Abstract:
The serum ratios of the brain‐specific oxysterol 24S‐hydroxycholesterol (24S‐OHC) to cholesterol and to 27‐OHC reflect brain cholesterol turnover. We studied the effect of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies ( PCSK9ab ) that enhance low‐density lipoprotein receptor activity on serum cholesterol and oxysterol concentrations. Methods Twenty‐eight hypercholesterolaemic patients (15 males and 13 females) responding insufficiently to maximally tolerated statin and/or ezetimibe therapy were additionally subcutanously treated biweekly with either the PCSK9ab alirocumab (150 mg, n = 13) or evolocumab (140 mg, n = 15). Fasting serum cholesterol was measured by gas chromatography and the oxysterols 24S‐OHC and 27‐OHC using gas chromatography–mass spectrometry before, after 1‐month ( n = 28) and after 3‐month ( n = 13) treatment. Results As expected, PCSK9ab treatment lowered serum cholesterol and oxysterol levels after 1 month. The serum ratio of 24S‐OHC to cholesterol increased after 1 month by 17 ± 28% (mean ± standard deviation; 95% confidence interval [CI]: 5.8 to 28%; P 〈 .01) and 24S‐OHC to 27‐OHC by 15 ± 39% (95% CI: 0.2 to 30%; P 〈 .01). Within 3 months, 24S‐OHC to cholesterol increased by 2.8 μg g −1 mo −1 (95% CI: 2.1 to 3.6; P 〈 .01) and 24S‐OHC to 27‐OHC by 0.019 mo −1 (95% CI: 0.007 to 0.032; P 〈 .01). Conclusion The serum ratios of 24S‐OHC to cholesterol and to 27‐OHC increased after treatment with PCSK9ab. We hypothesize that this is caused by a reduced entrance of 27‐OHC into the brain, increased synthesis of brain cholesterol, increased production of 24S‐OHC and its secretion across the blood–brain barrier.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
1498142-7
SSG:
15,3
