Danyu Wu1,2,3, Yajie Pan1,2,3, Shijun Yang1,2,3, Chang Li1,2,3, Yanzhao Zhou1,2,3, Yingxuan Wang1,2,3, Xiao Chen1,2,3, Zihua Zhou1,2,3, Yuhua Liao4,5,6, Zhihua Qiu7,8,9. 1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. 2. Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. 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. 4. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. liaoyh27@163.com. 5. Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. liaoyh27@163.com. 6. 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. liaoyh27@163.com. 7. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. qiu_zhihua512@163.com. 8. Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, China. qiu_zhihua512@163.com. 9. 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. qiu_zhihua512@163.com.
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.
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.
Entities:
Keywords:
Atherosclerosis; Hyperlipidemia; Liver X receptors; PCSK9; Vaccine
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