Evaluation of the effects of immunization against PCSK9 on selected microRNAs involved in cholesterol homeostasis

Abstract Background MicroRNAs (miRNAs) have been discovered as novel modulators of gene expression. These molecules are involved in regulating lipid metabolism through a complicated interactive mechanism involving regulatory networks and can play role metabolic diseases. PCSK9 (proprotein convertase subtilisin/Kexin 9) is critical regulator cholesterol homeostasis. inhibition an effective therapeutic strategy for the treatment dyslipidemia. Accordingly, it essential to identify controlling mechanisms effects its inhibitors on microRNAs Purpose Considering that miR-27a, miR-30c, miR-191 genes homeostasis, we investigated effect immunization against mentioned miRNAs. Methods A immunogenic peptide constructed by linking short mimotope tetanus was used immunization. The construct mixed homogeneously with 0.4% alum adjuvant at ratio 1:1 use vaccine formulation. Mice vaccinated group were inoculated subcutaneously four terms bi-weekly intervals. In order assess expression miRNAs mice' livers, sampling carried out two weeks after last injection. levels liver mice evaluated using real-time quantitative PCR, relative presented fold change normalized U6 internal control. Results Hepatic miR-27a significantly decreased compared control (fold change: 0.731±0.1, p=0.027). There borderline nonsignificant reduction hepatic miR-30c 0.569±0.1, p=0.078). No significant difference detected between groups 0.852±0.1, p=0.343). Conclusions Immunization leads miR-27a. Since regulation targets like angiopoietin-like 3 glycerol-3-phosphate acyltransferase 1, may explain part lipid-lowering activity vaccine. Funding Acknowledgement Type funding sources: None.