Over one-third of deaths worldwide are due to cardiovascular diseases, representing a critical global health crisis. Annually, these conditions cause 18.6 million deaths, with ischemic heart disease (IHD) responsible for nearly half, making it the top cause of death worldwide1,2. About 523 million people live with cardiovascular conditions, including 197 million with congenital heart defects. The overall impact results in the loss of 393 million disability-adjusted life years each year. In the United States, direct healthcare expenses and productivity losses related to these diseases exceed 352 billion US dollars annually, significantly affecting the economy. The European Union faces similar costs, estimated at 255 billion US dollars annually3. These health challenges are exacerbated by global trends such as population growth, the adoption of Westernized lifestyles, and an aging population4. Recent reviews highlight atherosclerosis as the key pathological process underlying most cardiovascular diseases.

To date, approximately 140 unique chemical modifications have been identified in RNA molecules5. RNA methylation involves adding methyl groups to specific nucleotide residues, such as N1-methyladenosine (m1A), N6-methyladenosine (m6A), N6,2’-O-dimethyladenosine (m6Am), and 2’-O-methylation6, 7, 8. The N6-methylation (m6A) of adenosine residues in mRNA has been extensively studied since its discovery in the 1970s9. This is the most common methylation in eukaryotic mRNA sequences and also the most abundant and evolutionarily conserved retrograde modification10. Functionally, m6A plays roles in various aspects of RNA biology, including regulating RNA stability, nuclear export, translation efficiency, and mRNA degradation pathways11,12. Besides its regulatory effects on protein-coding sequences (mRNAs), m6A methylation also affects non-coding RNA species such as microRNAs, long non-coding RNAs, and circular RNAs, thereby impacting gene expression during different physiological processes13,14.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, and their pathogenesis is complex and intricate. Although significant progress has been made in the diagnosis, treatment, and assessment of prognosis for cardiovascular diseases (CVD), there is an urgent need for innovative diagnostic biomarkers and treatment strategies in clinical practice to reduce the mortality rate of CVD patients and improve treatment outcomes. This review examines the relationship between m6A methylation modifications and cardiovascular diseases, synthesizing current understanding of associated regulatory pathways to identify potential therapeutic targets and novel treatment approaches.