International Journal of Molecular Sciences (Jun 2021)
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 Savinainen,
- Maciej 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
Affiliations
- Vilbert Sikorski
- Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Pasi Karjalainen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Daria Blokhina
- Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Kati Oksaharju
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Jahangir Khan
- Tampere Heart Hospital, Tampere University Hospital, 33520 Tampere, Finland
- Shintaro Katayama
- Folkhälsan Research Center, 00250 Helsinki, Finland
- Helena Rajala
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Satu Suihko
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Suvi Tuohinen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Kari Teittinen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Annu Nummi
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Antti Nykänen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Arda Eskin
- Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, 06800 Ankara, Turkey
- Christoffer Stark
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Fausto Biancari
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Jan Kiss
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Jarmo Simpanen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Jussi Ropponen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Karl Lemström
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Kimmo Savinainen
- Clinical Biobank Tampere, Tampere University Hospital, 33520 Tampere, Finland
- Maciej Lalowski
- Helsinki Institute of Life Science (HiLIFE), Meilahti Clinical Proteomics Core Facility, Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
- Markku Kaarne
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Mikko Jormalainen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Outi Elomaa
- Folkhälsan Research Center, 00250 Helsinki, Finland
- Pertti Koivisto
- Chemistry Unit, Finnish Food Authority, 00790 Helsinki, Finland
- Peter Raivio
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Pia Bäckström
- Helsinki Biobank, Hospital District of Helsinki and Uusimaa, 00029 Helsinki, Finland
- Sebastian Dahlbacka
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Simo Syrjälä
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Tiina Vainikka
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Tommi Vähäsilta
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Nurcan Tuncbag
- Department of Chemical and Biological Engineering, College of Engineering, Koç University, 34450 Istanbul, Turkey
- Mati Karelson
- Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia
- Eero Mervaala
- Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Tatu Juvonen
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Mika Laine
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Jari Laurikka
- Tampere Heart Hospital, Tampere University Hospital, 33520 Tampere, Finland
- Antti Vento
- Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland
- Esko Kankuri
- Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- DOI
- https://doi.org/10.3390/ijms22126630
- Journal volume & issue
-
Vol. 22,
no. 12
p. 6630
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.
Keywords
- biomarkers
- epitranscriptomics
- ischemic heart disease
- N<sup>6</sup>-methyladenosine
- m<sup>6</sup>A
- adenosine-to-inosine