In our study, ApoE mice were fed a high-fat diet for 12 weeks from 8 to 20 weeks of age. Then, using a repetitive multiple site strategy, the mice were immunized with a Keyhole limpet haemocyanin (KLH) conjugated G3BP2 peptide for 2 weeks from weeks 16 to 18. High levels of G3BP2 antibodies were detectable before sacrifice. Histological analyses showed that the number of atherosclerotic lesions in ApoE mice was significantly reduced following G3BP2 immunotherapy. The levels of pro-inflammatory cytokines and macrophages were also greatly decreased, while the collagen content of the plaques showed significant increase. Furthermore, knocking down G3BP2 in ApoE mice reduced the number of lesions compared to ApoE mice fed a high-fat diet for eight weeks. In vitro studies demonstrated that G3BP2 regulated ox-LDL-induced inflammation in HUVECs via controlling the localization of IκBα.
Immunization with the G3BP2 peptide antigen or knocking down of G3BP2 significantly decreased early atherosclerotic plaques in the ApoE mouse model of atherosclerosis. G3BP2 is a promising potential target for atherosclerosis therapy.
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