The effect of PCSK9 immunization on the hepatic level of microRNAs associated with the PCSK9/LDLR pathway

IntroductionWe aimed aimed to assess the effect of the immunotherapy with the PCSK9 peptide vaccine on the hepatic expression levels of microRNAs associated with LDLR pathway including miRNA-27a, miRNA-30c, and miRNA-191 in normal vaccinated mice.Material and methodsPCSK9 immunogenic peptide and 0.4% alum adjuvant were mixed at a 1:1 ratio and used as a vaccine formulation. Male albino mice were randomly assigned into vaccine or control groups. Mice in the vaccine group were injected four times at two-week intervals with a PCSK9 peptide vaccine, and mice in the control group were injected with phosphate-buffered saline. Animal livers were sampled two weeks after the last injection to assess miRNAs expression levels. The hepatic expression level of miRNA-27a, miRNA-30c, and miRNA-191 were evaluated by SYBR Green Real-Time PCR, quantified by comparative (2-ΔΔCT) method (Fold change) and normalized to U6 small nuclear RNA expression as an internal control.ResultsThe hepatic expression level of miRNA-27a showed significant reduction in mice following immunotherapy with the PCSK9 peptide vaccine when compared to the control group (FC:0.731±0.1, P=0.027). Also, there was a borderline significant reduction in the hepatic expression level of miRNA-30c in the vaccinated group compared to the control (FC: 0.569±0.1, P=0.078). However, no significant differences were found in the hepatic expression level of miRNA-191 between two studied groups (FC: 0.852±0.1, P=0.343).ConclusionsAccording to the findings, the PCSK9 peptide vaccine could effectively reduce the hepatic expression level of miRNA-27a and may be helpful in the management of LDL-C level and atherosclerosis, which may be mediated through LDLR pathway.