Escher, Geneviève; Zurkinden, Line; Mistry, H; Mansour, Y; Rohrbach, B; Vogt, Bruno (2016). Hepatic caveolin-1 is enhanced in Cyp27a1/ApoE double knockout mice. FEBS Open Bio, 6(10), pp. 1025-1035. Wiley 10.1002/2211-5463.12123
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Sterol 27-hydroxylase (CYP27A1) is involved in bile acid synthesis and cholesterol homoeostasis. Cyp27a1(-/-)/Apolipoprotein E(-/-) double knockout mice (DKO) fed a western diet failed to develop atherosclerosis. Caveolin-1 (CAV-1), the main component of caveolae, is associated with lipid homoeostasis and has regulatory roles in vascular diseases. We hypothesized that liver CAV-1 would contribute to the athero-protective mechanism in DKO mice. Cyp27a1(+/+)/ApoE(-/-) (ApoE KO), Cyp27a1(+/-)/ApoE(-/-) (het), and DKO mice were fed a western diet for 2 months. Atherosclerotic plaque and CAV-1 protein were quantified in aortas. Hepatic Cav-1 mRNA was assessed using qPCR, CAV-1 protein by immunohistochemistry and western blotting. Total hepatic and plasma cholesterol was measured using chemiluminescence. Cholesterol efflux was performed in RAW264.7 cells, using mice plasma as acceptor. CAV-1 protein expression in aortas was increased in endothelial cells of DKO mice and negatively correlated with plaque surface (P < 0.05). In the liver, both CAV-1 protein and mRNA expression doubled in DKO, compared to ApoE KO and het mice (P < 0.001 for both) and was negatively correlated with total hepatic cholesterol (P < 0.05). Plasma from DKO, ApoE KO and het mice had the same efflux capacity. In the absence of CYP27A1, CAV-1 overexpression might have an additional athero-protective role by partly overcoming the defect in CYP27A1-mediated cholesterol efflux.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie |
UniBE Contributor: |
Escher, Geneviève, Zurkinden, Line, Vogt, Bruno |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2211-5463 |
Publisher: |
Wiley |
Funders: |
[UNSPECIFIED] MRC Studentship ; [UNSPECIFIED] ERA-EDTA Fellowship ; [UNSPECIFIED] British Heart |
Language: |
English |
Submitter: |
Geneviève Escher |
Date Deposited: |
10 Feb 2017 14:07 |
Last Modified: |
05 Dec 2022 15:02 |
Publisher DOI: |
10.1002/2211-5463.12123 |
PubMed ID: |
28149711 |
Uncontrolled Keywords: |
atherosclerosis; cholesterol efflux; cholesterol metabolism; liver |
BORIS DOI: |
10.7892/boris.94886 |
URI: |
https://boris.unibe.ch/id/eprint/94886 |
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