Epitranscriptomics of ischemic heart disease-the IHD-EPITRAN study design and objectives

Vilbert Sikorski, Pasi Karjalainen, Daria Blokhina, Kati Oksaharju, Jahangir Khan, Shintaro Katayama, Helena Rajala, Satu Suihko, Suvi Tuohinen, Kari Teittinen, Annu Nummi, Antti Nykänen, Arda Eskin, Christoffer Stark, Fausto Biancari, Jan Kiss, Jarmo Simpanen, Jussi Ropponen, Karl Lemström, Kimmo SavinainenMaciej Lalowski, Markku Kaarne, Mikko Jormalainen, Outi Elomaa, Pertti Koivisto, Peter Raivio, Pia Bäckström, Sebastian Dahlbacka, Simo Syrjälä, Tiina Vainikka, Tommi Vähäsilta, Nurcan Tuncbag, Mati Karelson, Eero Mervaala, Tatu Juvonen, Mika Laine, Jari Laurikka, Antti Vento, Esko Kankuri

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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.

Original languageEnglish
Article number6630
JournalInternational Journal of Molecular Sciences
Volume22
Issue number12
DOIs
Publication statusPublished - Jun 2021
Publication typeA1 Journal article-refereed

Keywords

  • A-to-I
  • Adenosine-to-inosine
  • Biomarkers
  • Epitranscriptomics
  • Ischemic heart disease
  • M6A
  • N6-methyladenosine
  • RNA modifications

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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