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Updated: Oct 18, 2026

Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Dietary and hypothyroid hypercholesterolemia induces hepatic apolipoprotein E expression in the rat: direct role of
M Santillo1, A Migliaro, P Mondola
1Dipartimento di Neuroscienze e della Comunicazione Interumana-Sezione di Fisiologia, Università di Napoli 'Federico II', Napoli, Italy.
Abstract:
Apolipoprotein E (apo E) exerts a protective effect against atherosclerosis, related to its role in intracellular cholesterol removal and remnants clearance. In this study we investigated the effect of dietary and hypothyroid hypercholesterolemia, induced respectively by a high cholesterol diet and by propylthiouracil, on hepatic apo E expression in Wistar male rats. The Northern and Western blot analysis of hepatic mRNA and protein levels showed a 2-3-fold increase of apo E in hypercholesterolemic rats compared to controls. The incubation of FAO rat hepatoma cells with 25-OH cholesterol and mevalonate led to a three-fold increase of apo E mRNA, demonstrating a direct role of cholesterol on apo E expression. This effect was completely abolished by elevating intracellular cAMP levels with forskolin. Immunoblot and immunofluorescence analysis revealed that 25-OH cholesterol/mevalonate strongly increased also apo E protein synthesis and secretion in FAO cells. Our data demonstrate that hypercholesterolemia, apart of the cause (diet or hypothyroidism) induces liver apo E expression in the rat and that this effect can be directly related, via cAMP, to cholesterol.
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