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PCSK9Qβ-003 Vaccine Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice

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Abstract

Purpose

Our group has developed a therapeutic vaccine targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), named PCSK9Qβ-003. In this study, we investigated the potential effectiveness of the PCSK9Qβ-003 vaccine on atherosclerosis.

Methods

Male ApoE−/− mice were randomly assigned to three groups: a phosphate-buffered saline (PBS) group, Qβ virus-like particles (VLP) group, and PCSK9Qβ-003 vaccine group. Mice in the PCSK9Qβ-003 group were injected with the PCSK9Qβ-003 vaccine four times (100 μg/time) over a period of 18 weeks. The effects of the vaccine on atherosclerotic plaque, cholesterol transport, inflammation and apoptosis were investigated.

Results

The PCSK9Qβ-003 vaccine obviously decreased total cholesterol and low-density lipoprotein cholesterol in ApoE−/− mice. Compared with the other groups, the PCSK9Qβ-003 vaccine significantly reduced the lesion area and promoted the stability of atherosclerotic plaque. The vaccine regulated cholesterol transport in the aorta of ApoE−/− mice by up-regulating the expression level of liver X receptor α and ATP binding cassette transporter A1. Additionally, macrophage infiltration and expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α were significantly decreased in the mice administered the PCSK9Qβ-003 vaccine. The vaccine also markedly reduced apoptosis in the lesion area of the aorta in ApoE−/− mice.

Conclusions

The results demonstrated that the PCSK9Qβ-003 vaccine attenuated the progression of atherosclerosis by modulating reverse cholesterol transport and inhibiting inflammation infiltration and apoptosis, which may provide a novel therapeutic approach for atherosclerosis and greatly improve treatment compliance among patients.

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Funding

This study was funded by the Major Research Plan of the National Natural Science Foundation of China (no. 91439207) and the National Natural Science Foundation of China (nos. 81900401, 81900459, 81670461 and 81500388).

Author information

Author notes

  1. Danyu Wu, Yajie Pan and Shijun Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China

    Danyu Wu, Yajie Pan, Shijun Yang, Chang Li, Yanzhao Zhou, Yingxuan Wang, Xiao Chen, Zihua Zhou, Yuhua Liao & Zhihua Qiu

  2. Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China

    Danyu Wu, Yajie Pan, Shijun Yang, Chang Li, Yanzhao Zhou, Yingxuan Wang, Xiao Chen, Zihua Zhou, Yuhua Liao & Zhihua Qiu

  3. Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China

    Danyu Wu, Yajie Pan, Shijun Yang, Chang Li, Yanzhao Zhou, Yingxuan Wang, Xiao Chen, Zihua Zhou, Yuhua Liao & Zhihua Qiu

Authors
  1. Danyu Wu
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  2. Yajie Pan
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  4. Chang Li
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  8. Zihua Zhou
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  9. Yuhua Liao
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  10. Zhihua Qiu
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Corresponding authors

Correspondence to Yuhua Liao or Zhihua Qiu.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Informed consent was obtained from all individual participants included in the study.

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Wu, D., Pan, Y., Yang, S. et al. PCSK9Qβ-003 Vaccine Attenuates Atherosclerosis in Apolipoprotein E-Deficient Mice. Cardiovasc Drugs Ther 35, 141–151 (2021). https://doi.org/10.1007/s10557-020-07041-6

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