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Hepatic caveolin-1 is enhanced in Cyp27A1/ApoE double knockout mice

Zurkinden, Line; Mansour, Yosef; Rohrbach, Beatrice; Vogt, Bruno; Mistry, Hiten D.; Escher, Genevieve

Authors

Line Zurkinden

Yosef Mansour

Beatrice Rohrbach

Bruno Vogt

Hiten D. Mistry hiten.mistry@nottingham.ac.uk

Genevieve Escher



Abstract

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.

Journal Article Type Article
Publication Date Oct 1, 2016
Journal FEBS Open Bio
Electronic ISSN 2211-5463
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 6
Issue 10
APA6 Citation Zurkinden, L., Mansour, Y., Rohrbach, B., Vogt, B., Mistry, H. D., & Escher, G. (2016). Hepatic caveolin-1 is enhanced in Cyp27A1/ApoE double knockout mice. FEBS Open Bio, 6(10), https://doi.org/10.1002/2211-5463.12123
DOI https://doi.org/10.1002/2211-5463.12123
Publisher URL http://onlinelibrary.wiley.com/doi/10.1002/2211-5463.12123/full
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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