Epitranscriptome: A Novel Regulatory Layer during Atherosclerosis Progression

Area of Science:

• Molecular Biology
• Genetics
• Cardiology

Background:

• RNA modifications, collectively termed the epitranscriptome, play crucial regulatory roles in cellular processes.
• Alterations in the epitranscriptome are increasingly recognized in cardiovascular diseases (CVDs), including atherosclerosis (AS).
• The precise transcriptional and post-transcriptional regulatory mechanisms of epitranscriptome changes in AS remain largely unexplored.

Purpose of the Study:

• To review the main epitranscriptome modifications implicated in AS.
• To discuss current RNA modifier-targeting strategies and potential therapeutic molecules.
• To highlight the potential of epitranscriptome pathways as biomarkers and therapeutic targets for AS.

Main Methods:

• Comprehensive literature review of epitranscriptome modifications (m6A, m5C, m1A, m7G, Ψ, A-to-I editing) in AS.
• Analysis of current small molecule inhibitors and activators targeting RNA modification enzymes (e.g., METTL3, FTO, ALKBH5).
• Exploration of identified phytomolecules (e.g., Panax notoginseng saponins, rhein) with potential epitranscriptome-modulating effects.

Main Results:

• Key epitranscriptome signatures, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), and others, are associated with AS.
• Small molecules targeting enzymes like FTO show promise in modulating RNA modifications.
• Phytomolecules such as rhein have demonstrated potential as FTO inhibitors, increasing mRNA m6A levels.

Conclusions:

• Epitranscriptome pathways are significantly implicated in the pathogenesis of AS.
• Targeting RNA epitranscriptome modifications presents novel opportunities for developing predictive, diagnostic, and prognostic biomarkers.
• Further research into epitranscriptome-sensitive pathways could lead to new precision medicine strategies for CVDs.