Abstract
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•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.
Results
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).
Conclusion
Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR- α and PCSK9 in ApoE-/- mice.
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Shen DZ, Li SS conceived and designed the study and performed the experiments. Li SS, Cao H and Jia QL made substantial contributions to the acquisition, analysis and interpretation of the data and wrote the paper. Shen DZ, Chen C, Xing SL and Dou FF reviewed and edited the manuscript. All authors read and approved the manuscript.
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Supported by the National Natural Science Foundation of China (No. 81202731, 81873348), the Shanghai Nature Science Fund (No. 16ZR1433900), the Shanghai Health and Family Planning Commission Fund (No. 201640217) and Shanghai University of Traditional Chinese Medicine Graduate “Innovation Ability Training” Special Research Projects (No. Y201858)
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Li, Ss., Cao, H., Shen, Dz. et al. Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- Mice. Chin. J. Integr. Med. 26, 114–121 (2020). https://doi.org/10.1007/s11655-019-2942-9
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DOI: https://doi.org/10.1007/s11655-019-2942-9