Pcsk9q Beta-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 PCSK9Q beta-003. In this study, we investigated the potential effectiveness of the PCSK9Q beta-003 vaccine on atherosclerosis. Methods Male ApoE(-/-)mice were randomly assigned to three groups: a phosphate-buffered saline (PBS) group, Q beta virus-like particles (VLP) group, and PCSK9Q beta-003 vaccine group. Mice in the PCSK9Q beta-003 group were injected with the PCSK9Q beta-003 vaccine four times (100 mu g/time) over a period of 18 weeks. The effects of the vaccine on atherosclerotic plaque, cholesterol transport, inflammation and apoptosis were investigated. Results The PCSK9Q beta-003 vaccine obviously decreased total cholesterol and low-density lipoprotein cholesterol in ApoE(-/-)mice. Compared with the other groups, the PCSK9Q beta-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 alpha and ATP binding cassette transporter A1. Additionally, macrophage infiltration and expression of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha were significantly decreased in the mice administered the PCSK9Q beta-003 vaccine. The vaccine also markedly reduced apoptosis in the lesion area of the aorta in ApoE(-/-)mice. Conclusions The results demonstrated that the PCSK9Q beta-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.