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 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.