COL6A6 peptide vaccine ameliorates atherosclerosis through inducing immune response and regulating lipid metabolism in ApoE-/- mice

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels with limited preventive and treatment options currently available. Previous experiments have demonstrated the atheroprotective potential of collagen 6 subtype alpha6 (COL6A6) in apolipoprotein E-deficient (ApoE-/-) mice with hyperlipidemia. However, the mechanism underlying the anti-atherosclerotic effects of COL6A6 remains elusive. This knowledge gap was addressed in the present study by immunizing ApoE-/- mice with the Pep_A6 vaccine, comprising a COL6A6 peptide-KLH (keyhole limpet hemocyanin) conjugate and aluminum (Alum) hydroxide adjuvant, and conducting a series of experiments. Our objective was to investigate the efficacy of the Pep_A6 vaccine, focusing on immune responses and lipid metabolism. Our finding showed that the Pep_A6 vaccine represents a novel approach to combat atherosclerosis by inducing a large increase in Treg cells, the generation of antigen-specific antibodies and regulating lipid metabolism. Overall design: To investigate the effect of vaccine on lipid metabolism, livers were collected from ApoE-/- mice subjected to a normal diet or a high-fat diet immunized with the Pep_A6 vaccine or PBS. Each group contained 3-5 replicates, and subsequently the samples were analyzed by transcriptome sequencing. The high-fat diet was fed for 20 weeks, and the Chow mice, as the normal control group, was continuously fed a normal diet throughout the study period.