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

Abstract

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.

Functional roles of epitranscriptomic marks in the cardiovascular system and disease: a narrative review

“…This new field of study extends further understanding of epigenetics from the perspective of RNA, where the terminologies are adopted from epigenetics, including writers, readers, and erasers to categorize epitranscriptomic enzymes. These enzymes are active in many tissues and cell types, whose dyregulations are linked to a variety of disorders and critical diseases, such as cardiovascular disease ( 9 , 10 ). These epitranscriptomic enzymes mark all kinds of RNA species, including mRNAs and ncRNAs, such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), miRNAs, and lncRNAs ( 11 ).…”

Emerging roles of the RNA modifications N6-methyladenosine and adenosine-to-inosine in cardiovascular diseases

“…Prospective controlled observational cohort studies, such as the The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study ( www.ihd-epitran.com ), help us to shed light into this fascinating development. 412 …”

Epitranscriptome in Ischemic Cardiovascular Disease: Potential Target for Therapies

“…In addition, recent studies have also shown the m 6 A-methylation landscape of human CAD and aortic dissection. 62,63 A 2019 study showed that C57BL/6J mice subjected to transient middle cerebral artery occlusion displayed increased total m 6 A levels after 12 and 24 hours of reperfusion compared with sham operated animals. 64 The authors of this study demonstrated the presence of differentially hyper- and hypo-methylated mRNAs and long noncoding RNAs belonging to biological processes associated with inflammation, apoptosis, and transcriptional regulation after stroke.…”