Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- Mice.

Abstract

To investigate the effect of quercetin on ATP binding cassette transporter A1 (ABCA1), liver X receptor (LXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions in apoE-knockout (ApoE-/-) mice. The high-fat diet-induced atherosclerosis (AS) in ApoE-/- mice was established. Thirty-six mice were divided into 3 groups using random number table method: model group (n=12), quercetin group (n=12), and atorvastatin group (n=12), with C57BL/6J mice of the same strain and age as the control group (n=12). Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage, with doses of 12.5 and 4 mg/(kg•d), respectively. Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks. Western blot and immunohistochemical methods were employed to determine the aortic ABCA1, LXR-α and PCSK9 protein expression. Enzyme linked immunosorbent assay method was used to detect the expression of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10, combined with tissue pathological examination. ApoE-/- mice fed with a high-fat diet had notable atherosclerosis lesions, with reduced ABCA1, LXR-α and IL-10 levels (all P<0.01), elevated PCSK9, TNF-α and IL-6 expression, and increased TC and LDL-C contents (all P<0.01). After quercetin intervention, the areas of AS plaques and the expressions of PCSK9, TNF-α and IL-6 were significantly reduced (all P<0.01), while the expressions of ABCA1 and LXR-α were increased significantly (all P<0.01). Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR- α and PCSK9 in ApoE-/- mice.