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The effect of PCSK9 immunization on the hepatic level of microRNAs associated with the PCSK9/LDLR pathway
Sarina Ataei1,2, Shiva Ganjali3, Maciej Banach4,5
1Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Introduction:
MicroRNAs (miRNAs) are a class of gene expression epigenetic regulators that play roles in regulating genes involved in cholesterol homeostasis, including low-density lipoprotein receptor (LDLR) and PCSK9; therefore, miRNAs have been suggested as potential therapeutic targets for treating cardiometabolic disorders. Thus, the present study aimed to assess the effect of immunotherapy with the PCSK9 peptide vaccine on the hepatic expression levels of microRNAs associated with the LDLR pathway, including miRNA-27a, miRNA-30c, and miRNA-191, in normal vaccinated mice.
Material And Methods:
PCSK9 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 to the vaccine or control group. 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 (PBS). Animal livers were sampled 2 weeks after the last injection to assess miRNA expression levels. The hepatic expression levels of miRNA-27a, miRNA-30c, and miRNA-191 were evaluated by SYBR Green real-time PCR, quantified by a comparative (2- Δ Δ CT) method (fold change (FC)) and normalized to U6 small nuclear RNA (U6snRNA) expression as an internal control.
Results:
The hepatic expression level of miRNA-27a was significantly lower in mice following immunotherapy with the PCSK9 peptide vaccine compared to the control group (FC: 0.731 ±0.1, p = 0.027). Also, there was a borderline significantly lower 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 the two studied groups (FC: 0.852 ±0.1, p = 0.343).
Conclusions:
According 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 the LDLR pathway.
Insights
Immunotherapy with a PCSK9 peptide vaccine significantly reduced hepatic miRNA-27a levels in mice. This suggests potential for managing cholesterol and atherosclerosis via the low-density lipoprotein receptor pathway.
Area of Science:
- Cardiovascular Science
- Molecular Biology
- Immunology
Background:
- MicroRNAs (miRNAs) are epigenetic regulators influencing cholesterol homeostasis.
- Genes like low-density lipoprotein receptor (LDLR) and PCSK9 are key in cholesterol regulation.
- miRNAs are explored as therapeutic targets for cardiometabolic disorders.
Purpose of the Study:
- To evaluate the impact of a PCSK9 peptide vaccine on hepatic microRNA expression.
- Specifically assessed were miRNAs involved in the LDLR pathway: miRNA-27a, miRNA-30c, and miRNA-191.
- The study was conducted in normal mice receiving immunotherapy.
Main Methods:
- A vaccine formulation containing PCSK9 immunogenic peptide and alum adjuvant was administered.
- Male albino mice were divided into vaccine and control (PBS) groups.
- Livers were sampled post-vaccination for miRNA analysis using SYBR Green real-time PCR.
Main Results:
- Hepatic miRNA-27a expression was significantly lower in the vaccinated group (FC: 0.731, p=0.027).
- A trend towards lower miRNA-30c expression was observed (FC: 0.569, p=0.078).
- No significant difference in miRNA-191 expression was found between groups (FC: 0.852, p=0.343).
Conclusions:
- The PCSK9 peptide vaccine effectively reduced hepatic miRNA-27a levels.
- This suggests a potential role in managing LDL-C levels and atherosclerosis.
- The mechanism may involve modulation of the LDLR pathway.
