Correlation between methyltransferase METTL7B and atherosclerosis.

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Genetics

Background:

• Atherosclerosis (AS) poses a significant health risk, with connections to glucose balance, lipid metabolism, inflammation, and hypertension.
• The role of the methyltransferase-like (METTL) gene family in AS pathogenesis remains largely unexplored.

Purpose of the Study:

• To investigate the involvement of METTL family members in the occurrence and development of atherosclerosis.
• To identify potential diagnostic and therapeutic targets for AS within the METTL family.

Main Methods:

• Differential gene expression analysis of METTL family members in AS versus normal vascular tissues using public databases (GSE43292, GSE100927).
• Random forest screening to identify marker genes, followed by cross-database validation (GSE28829, GSE41571) and clinical sample analysis.
• Analysis of marker gene localization, correlation with lipid metabolism and efferocytosis, RNA sequencing, and targeted lipidomics.

Main Results:

• METTL7B and METTL5 were identified as intersection marker genes.
• METTL7B expression was significantly upregulated in advanced AS, ruptured plaques, and heavy-load plaques.
• METTL7B showed a strong correlation with lipid metabolism, promoted lipid droplet formation, and was linked to macrophage-mediated efferocytosis.

Conclusions:

• METTL7B plays a crucial role in the development of atherosclerosis by influencing lipid metabolism and efferocytosis.
• METTL7B demonstrates potential as a predictive biomarker and a therapeutic target for atherosclerosis.
• METTL7B regulates numerous lipids, mediated by specific genes, revealing a novel mechanism in AS pathogenesis.