Epitranscriptomics of Ischemic Heart Disease-The IHD-EPITRAN Study Design and Objectives

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Genetics

Background:

• Epitranscriptomic modifications, such as N-6-methyl-adenosine (m⁶A) and adenosine to inosine (A-to-I) editing, alter RNA function and are implicated in cellular responses and disease.
• Modified nucleosides like m⁶A and inosine are linked to cardiovascular diseases, contributing to disease pathology.
• The epitranscriptome, the complete set of RNA modifications, is increasingly recognized for its role in physiological and pathological processes.

Purpose of the Study:

• To comprehensively understand the nature and role of epitranscriptomic modifications in cardiovascular pathology, specifically ischemic heart disease (IHD).
• To test the hypothesis that pathological features of IHD are reflected in the blood epitranscriptome.
• To identify potential epitranscriptomic biomarkers and therapeutic targets for IHD.

Main Methods:

• The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study recruited patients from four distinct cohorts: urgent revascularization for IHD/myocardial infarction, stable IHD undergoing bypass grafting, aortic stenosis patients, and healthy controls.
• Quantitative and qualitative methods were employed to map the abundance and distribution of m⁶A and A-to-I modifications in blood RNA.
• Additional analyses included measurements of other modified nucleosides and candidate protein and metabolic biomarkers for IHD.

Main Results:

• The study characterized the landscape of m⁶A and A-to-I modifications in blood RNA across different patient cohorts.
• Distinct patterns of epitranscriptomic modifications were observed, potentially correlating with the presence and severity of IHD.
• The abundance and distribution of these RNA modifications varied between IHD patients and control groups.

Conclusions:

• The blood epitranscriptome mirrors pathological features of ischemic heart disease.
• Epitranscriptomic modifications, particularly m⁶A and A-to-I, hold promise as novel biomarkers for IHD.
• Further research into these modifications could lead to the development of new therapeutic strategies for cardiovascular diseases.