The Role of N6-Methyladenosine RNA Methylation in Cardiovascular Diseases: Molecular Mechanisms and Clinical Applications
Year: 2025
Type: article
Abstract: Cardiovascular diseases (CVDs), the leading cause of global mortality, demand novel therapeutic strategies targeting their molecular underpinnings. Emerging research underscores N6-methyladenosine (m6A) RNA methylation—a dynamic epigenetic modification orchestrated by writers (e.g., METTL3), erasers (e.g., FTO), and readers (e.g., YTHDF)—as a central regulator of CVD pathogenesis. By modulating RNA splicing, stability, and translation, m6A critically influences inflammation, fibrosis, and metabolic homeostasis. The dysregulation of this machinery drives pathologies such as atherosclerosis, where METTL3-mediated m6A hypermethylation stabilizes NLRP3 transcripts, exacerbating endothelial inflammation, and ischemic heart disease, where FTO-dependent demethylation of BCL2 enhances cardiomyocyte survival. Clinically, m6A-related genetic variants (e.g., FTO rs9939609) correlate with CVD susceptibility, while circulating m6A levels serve as the promising non-invasive biomarkers. Preclinical advances highlight therapeutic strategies, including FTO inhibitors (e.g., meclofenamic acid) and CRISPR-based m6A editing tools, though the challenges like off-target effects and delivery inefficiencies impede the clinical translation. Future priorities include resolving cell-type-specific m6A dynamics via single-cell sequencing, integrating multi-omics data to unravel the epigenetic crosstalk, and advancing the clinical trials for m6A-targeted therapies. By bridging the mechanistic insights with translational innovation, m6A epitranscriptomics offers a paradigm shift in CVD management, emphasizing interdisciplinary collaboration to overcome barriers and realize precision medicine tailored to the dynamic epigenetic landscapes.
Source: Theoretical and Natural Science
Author: Dede Kong
Institution: Tianjin Agricultural University
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4409777739