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

Objective 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. Methods 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 center dot 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-alpha 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-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10, combined with tissue pathological examination. Results ApoE(-/-) mice fed with a high-fat diet had notable atherosclerosis lesions, with reduced ABCA1, LXR-alpha and IL-10 levels (all P<0.01), elevated PCSK9, TNF-alpha 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-alpha and IL-6 were significantly reduced (all P<0.01), while the expressions of ABCA1 and LXR-alpha were increased significantly (all P<0.01). Conclusion Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR- alpha and PCSK9 in ApoE(-/-) mice.