Hepatic caveolin-1 is enhanced in Cyp27a1/ApoE double knockout mice

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)

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 and 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:

10 Feb 2017 14:07

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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