Publication:
Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice.

cris.virtual.author-orcid0000-0002-5125-2262
cris.virtualsource.author-orcid4fd2f7c2-7be6-49bb-99cb-b03db2efc9b7
cris.virtualsource.author-orcid80a53445-481b-4f42-8014-c3bfb5ee6f2e
datacite.rightsopen.access
dc.contributor.authorZurkinden, Line
dc.contributor.authorSviridov, Dmitri
dc.contributor.authorVogt, Bruno
dc.contributor.authorEscher, Geneviève
dc.date.accessioned2024-10-25T13:44:09Z
dc.date.available2024-10-25T13:44:09Z
dc.date.issued2018-02-28
dc.description.abstractSterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/ Apolipoprotein E (ApoE) double knockout (KO) mice fed with Western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ApoE KO (het) mice, with reduced Cyp27a1 expression and normal levels of Cyp7a1 and Cyp3a11, developed more severe lesions than ApoE KO mice. To analyze the contribution of Cyp3a11 to the protection of atherosclerosis development, Cyp3a11 was induced by Rifampicin (RIF) in ApoE KO and het mice. Males were fed with WD and treated daily with RIF (10 mg/kg ip) or vehicle for 4 weeks. Atherosclerosis was quantified in the aortic valve. Plasma lipids and 27-hydroxycholesterol (27-OHC), expression of cytochromes P450 and genes involved in cholesterol transport and bile acids (BAs) signaling in liver and intestine, and intestinal cholesterol absorption were analyzed. RIF increased expression of hepatic but not intestinal Cyp3a11 4-fold in both genotypes. In ApoE KO mice treated with RIF, we found a 2-fold decrease in plasma cholesterol, and a 2-fold increase in high-density lipoprotein/low-density lipoprotein ratio and CY27A1 activity. Intestinal cholesterol absorption remained unchanged and atherosclerotic lesions decreased approximately 3-fold. In het mice, RIF had no effect on plasma lipids composition, CYP27A1 activity, and atherosclerotic plaque development, despite a reduction in cholesterol absorption. In conclusion, the antiatherogenic effect of Cyp3a11 induction by RIF was also dependent on Cyp27a1 expression.
dc.description.sponsorshipUniversitätsklinik für Nephrologie und Hypertonie
dc.description.sponsorshipDepartment for BioMedical Research, Forschungsgruppe Nephrologie / Hypertonie
dc.identifier.doi10.7892/boris.110416
dc.identifier.pmid29191818
dc.identifier.publisherDOI10.1042/BSR20171162
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/157780
dc.language.isoen
dc.publisherPortland Press
dc.relation.ispartofBioscience reports
dc.relation.issn1573-4935
dc.relation.organizationDCD5A442BB17E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C268E17DE0405C82790C4DE2
dc.subject27-hydroxycholesterol ApoE knock out mice Western diet
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titleSterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice.
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.issue1
oaire.citation.volume38
oairecerif.author.affiliationUniversitätsklinik für Nephrologie und Hypertonie
oairecerif.author.affiliationDepartment for BioMedical Research, Forschungsgruppe Nephrologie / Hypertonie
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unibe.date.licenseChanged2019-10-27 20:42:26
unibe.description.ispublishedpub
unibe.eprints.legacyId110416
unibe.refereedtrue
unibe.subtype.articlejournal

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