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

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 thr...

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Bibliographic Details
Published in:Cardiovascular drugs and therapy 2021-02, Vol.35 (1), p.141-151
Main Authors: Wu, Danyu, Pan, Yajie, Yang, Shijun, Li, Chang, Zhou, Yanzhao, Wang, Yingxuan, Chen, Xiao, Zhou, Zihua, Liao, Yuhua, Qiu, Zhihua
Format: Article
Language:English
Subjects:
Aorta
Apolipoprotein E
Apoptosis
Arteriosclerosis
Atherosclerosis
Cardiology
Cholesterol
Coronary vessels
Infiltration
Inflammation
Kexin
Lesions
Liver X receptors
Macrophages
Medicine
Medicine & Public Health
Metastases
Monocyte chemoattractant protein
Monocyte chemoattractant protein 1
Monocytes
Original Article
Proprotein convertases
Subtilisin
Tumor necrosis factor-α
Vaccines
Virus-like particles
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Summary: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.
ISSN:0920-3206
1573-7241
DOI:10.1007/s10557-020-07041-6