Hepatic caveolin-1 is enhanced inCyp27a1/ApoEdouble knockout mice.
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. HepaticCav-1mRNA 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.
Department of Nephrology, Hypertension, Clinical Pharmacology and Clinical Research University of Bern Switzerland.
Line
L
Zurkinden
Division of Women's Health King's College London Women's Health Academic Centre UK.
Yosef T
YT
Mansour
Department of Nephrology, Hypertension, Clinical Pharmacology and Clinical Research University of Bern Switzerland.
Beatrice
B
Rohrbach
Department of Nephrology, Hypertension, Clinical Pharmacology and Clinical Research University of Bern Switzerland.
Bruno
B
Vogt
Department of Nephrology, Hypertension, Clinical Pharmacology and Clinical Research University of Bern Switzerland; Division of Child Health, Obstetrics & Gynaecology School of Medicine University of Nottingham UK.
Hiten D
HD
Mistry
Department of Nephrology, Hypertension, Clinical Pharmacology and Clinical Research University of Bern Switzerland.
Geneviève
G
Escher
atherosclerosis; cholesterol efflux; cholesterol metabolism; liver