Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome

Severi Mulari; Arda Eskin; Milla Lampinen; Annu Nummi; Tuomo Nieminen; Kari Teittinen; Teija Ojala; Matti Kankainen; Antti Vento; Jari Laurikka; Markku Kupari; Ari Harjula; Nurcan Tuncbag; Esko Kankuri

doi:10.3389/fcvm.2021.728198

Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome

Front Cardiovasc Med. 2021 Dec 2:8:728198. doi: 10.3389/fcvm.2021.728198. eCollection 2021.

Authors

Severi Mulari^{1

2}, Arda Eskin³, Milla Lampinen^{1

4}, Annu Nummi², Tuomo Nieminen², Kari Teittinen², Teija Ojala¹, Matti Kankainen⁵, Antti Vento², Jari Laurikka^{6

7}, Markku Kupari², Ari Harjula², Nurcan Tuncbag^{3

8

9}, Esko Kankuri¹

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
² Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Department of Health Informatics, Graduate School of Informatics, Middle East Technical University (METU), Ankara, Turkey.
⁴ Department of Oral and Maxillofacial Diseases, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁵ Research Programs Unit, University of Helsinki, Helsinki, Finland.
⁶ Department of Cardiothoracic Surgery, Heart Center, Tampere University Hospital, Tampere, Finland.
⁷ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁸ Department of Chemical and Biological Engineering, College of Engineering, Koc University, Istanbul, Turkey.
⁹ School of Medicine, Koc University, Istanbul, Turkey.

Abstract

Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes. Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell-cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery. Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.

Keywords: atrial appendage; biomarkers; cardiovascular surgery; chronic ischemic heart disease; differentially expressed genes; ischemia.