Epitranscriptomic regulation in cardiovascula disease: mechanistic roles and clinical implications of m6A RNA methylation in cardiac pathophysiology.

N6-methyladenosine (m6A) RNA methylation has emerged as a pivotal epitranscriptomic regulator influencing cardiovascular development, homeostasis, and disease progression. As the most abundant internal modification in eukaryotic mRNA, m6A dynamically modulates RNA stability, translation, splicing, and degradation through the coordinated actions of "writers," "readers," and "erasers." Recent advances demonstrate that dysregulated m6A modifications contribute to major cardiovascular disorders, including cardiac hypertrophy, heart failure, arrhythmias, atherosclerosis, ischemia reperfusion injury, and cardiomyopathy. METTL3-mediated hypermethylation promotes pathological hypertrophy, autophagy imbalance, and ischemic injury. In contrast, demethylases such as FTO and ALKBH5 exert cardioprotective effects by preserving contractile function, enhancing angiogenesis, and regulating key transcripts involved in Ca²⁺ cycling, autophagy, and metabolism. m6A-dependent control of noncoding RNAs further amplifies its impact on inflammatory signaling, endothelial dysfunction, and vascular remodeling. The involvement of m6A in glucose metabolism, hypoxia responses, and vascular smooth muscle phenotypic transitions highlights its broad relevance across cardiovascular risk factors. As detection technologies advance, m6A profiling shows promise as a diagnostic biomarker and therapeutic target. Understanding epitranscriptomic regulation may unlock innovative treatment strategies and reshape the future of cardiovascular medicine.