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

International Journal of Molecular Sciences

Pertti Koivisto¹  Kimmo Savinainen²  Nurcan Tuncbag³  Daria Blokhina⁴  Esko Kankuri⁴  Eero Mervaala⁴  Vilbert Sikorski⁴  Outi Elomaa⁵  Shintaro Katayama⁵  Arda Eskin⁶  Jussi Ropponen⁷  Satu Suihko⁷  Kari Teittinen⁷  Suvi Tuohinen⁷  Mika Laine⁷  Fausto Biancari⁷  Tatu Juvonen⁷  Helena Rajala⁷  Karl Lemström⁷  Sebastian Dahlbacka⁷  Jarmo Simpanen⁷  Mikko Jormalainen⁷  Simo Syrjälä⁷  Antti Nykänen⁷  Jan Kiss⁷  Antti Vento⁷  Kati Oksaharju⁷  Markku Kaarne⁷  Annu Nummi⁷  Tiina Vainikka⁷  Christoffer Stark⁷  Pasi Karjalainen⁷  Tommi Vähäsilta⁷  Peter Raivio⁷  Pia Bäckström⁸  Maciej Lalowski⁹  Mati Karelson^1,10  Jari Laurikka^1,11  Jahangir Khan^1,11 

[1] Chemistry Unit, Finnish Food Authority, 00790 Helsinki, Finland;Clinical Biobank Tampere, Tampere University Hospital, 33520 Tampere, Finland;Department of Chemical and Biological Engineering, College of Engineering, Koç University, 34450 Istanbul, Turkey;Department of Pharmacology, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland;Folkhälsan Research Center, 00250 Helsinki, Finland;Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, 06800 Ankara, Turkey;Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland;Helsinki Biobank, Hospital District of Helsinki and Uusimaa, 00029 Helsinki, Finland;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;Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia;Tampere Heart Hospital, Tampere University Hospital, 33520 Tampere, Finland;

关键词: biomarkers;    epitranscriptomics;    ischemic heart disease;    N⁶-methyladenosine;    m⁶A;    adenosine-to-inosine;   

DOI  :  10.3390/ijms22126630

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown