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Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE‑/‑ mice

  • Authors:
    • Li Yan
    • Qingling Jia
    • Hui Cao
    • Chuan Chen
    • Sanli Xing
    • Yan Huang
    • Dingzhu Shen
  • View Affiliations / Copyright

    Affiliations: Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 25
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    Published online on: November 9, 2020
       https://doi.org/10.3892/etm.2020.9457
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Abstract

The purpose of the current study was to investigate the mechanism by which fisetin improves atherosclerosis (AS) by regulating lipid metabolism and senescence in apolipoprotein E‑deficient (apoE‑/‑) mice. An AS model was established by feeding apoE‑/‑ mice a high‑fat diet. Mice were randomly divided into the model group (n=18), the fisetin group (n=18) and the atorvastatin group (n=18). The control group (n=18) was composed of wild‑type C57BL/6 mice of the same age and genetic background. The fisetin and atorvastatin groups were respectively treated with aqueous solutions of fisetin (12.5 mg/kg) and atorvastatin (2 mg/kg) via oral gavage daily for 12 weeks. The pathological morphology, lipid accumulation, collagen deposition of the aortic sinus were observed, serum lipids, superoxide dismutase (SOD) and malondialdehyde (MDA) levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in the peripheral blood serum. Additionally, the expressions of proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin‑like oxidized low‑density lipoprotein receptor‑1 (LOX‑1), tumor suppressor protein p53 (p53), cyclin‑dependent kinase inhibitor 1A (p21) and multiple tumor suppressor‑1 (p16) were analyzed in the aorta. The results of the current study indicated that compared with the control group, a large area of AS plaque in the aortic sinus that contained a large amount of red‑stained lipids and decreased collagen fiber content were found in the model group, which exhibited higher total cholesterol (TC), low‑density lipoprotein cholesterol (LDL‑C), very low‑density lipoprotein cholesterol (VLDL‑C), oxidized low‑density lipoprotein (ox‑LDL) and MDA levels; higher ALT and AST activities, lower high‑density lipoprotein cholesterol (HDL‑C) and SOD levels and increased expression levels of PCSK9, LOX‑1, p53, p21 and p16. Fisetin is a phytochemical and bioflavonoid that serves a potential role in chronic diseases including AS, obesity, diabetes and cancer due to its wide biological activities, such as regulating lipid metabolism and anti‑aging, anti‑oxidation and anti‑inflammatory. Atorvastatin is recognized as a first‑line treatment drug for AS; therefore it was used as a positive control in the current study. Following fisetin and atorvastatin treatment, both the AS plaque and the lipid accumulation in the aortic sinus were significantly reduced, and the expressions of PCSK9, LOX‑1 and aging markers, including p53, p21 and p16 were downregulated.
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Copy and paste a formatted citation
Spandidos Publications style
Yan L, Jia Q, Cao H, Chen C, Xing S, Huang Y and Shen D: Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice. Exp Ther Med 21: 25, 2021.
APA
Yan, L., Jia, Q., Cao, H., Chen, C., Xing, S., Huang, Y., & Shen, D. (2021). Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice. Experimental and Therapeutic Medicine, 21, 25. https://doi.org/10.3892/etm.2020.9457
MLA
Yan, L., Jia, Q., Cao, H., Chen, C., Xing, S., Huang, Y., Shen, D."Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice". Experimental and Therapeutic Medicine 21.1 (2021): 25.
Chicago
Yan, L., Jia, Q., Cao, H., Chen, C., Xing, S., Huang, Y., Shen, D."Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice". Experimental and Therapeutic Medicine 21, no. 1 (2021): 25. https://doi.org/10.3892/etm.2020.9457
Copy and paste a formatted citation
x
Spandidos Publications style
Yan L, Jia Q, Cao H, Chen C, Xing S, Huang Y and Shen D: Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice. Exp Ther Med 21: 25, 2021.
APA
Yan, L., Jia, Q., Cao, H., Chen, C., Xing, S., Huang, Y., & Shen, D. (2021). Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice. Experimental and Therapeutic Medicine, 21, 25. https://doi.org/10.3892/etm.2020.9457
MLA
Yan, L., Jia, Q., Cao, H., Chen, C., Xing, S., Huang, Y., Shen, D."Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice". Experimental and Therapeutic Medicine 21.1 (2021): 25.
Chicago
Yan, L., Jia, Q., Cao, H., Chen, C., Xing, S., Huang, Y., Shen, D."Fisetin ameliorates atherosclerosis by regulating PCSK9 and LOX‑1 in apoE<sup>‑/‑</sup> mice". Experimental and Therapeutic Medicine 21, no. 1 (2021): 25. https://doi.org/10.3892/etm.2020.9457
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