1. Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
- Author
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Mulari, Severi, Eskin, Arda, Lampinen, Milla, Nummi, Annu, Nieminen, Tuomo, Teittinen, Kari, Ojala, Teija, Kankainen, Matti, Vento, Antti, Laurikka, Jari, Kupari, Markku, Harjula, Ari, Tuncbag, Nurcan, Kankuri, Esko, OpenMETU, Department of Pharmacology, HUS Heart and Lung Center, HUS Perioperative, Intensive Care and Pain Medicine, Department of Oral and Maxillofacial Diseases, Päijät-Häme Welfare Consortium, HYKS erva, HUSLAB, TRIMM - Translational Immunology Research Program, Research Programs Unit, Department of Surgery, Clinicum, III kirurgian klinikka, Department of Medicine, Esko Markus Kankuri / Principal Investigator, Medicum, Tampere University, Clinical Medicine, and TAYS Heart Centre
- Subjects
differentially expressed genes ,CARDIOMYOPATHY ,cardiovascular surgery ,IDENTIFICATION ,chronic ischemic heart disease ,BIOMARKERS ,atrial appendage ,PROLIFERATION ,ischemia ,Cardiovascular Medicine ,3121 Internal medicine ,3126 Surgery, anesthesiology, intensive care, radiology ,PHENOTYPE ,GENE ,INFLAMMATION ,CARDIOVASCULAR-DISEASE ,3121 General medicine, internal medicine and other clinical medicine ,cardiovascular system ,3111 Biomedicine ,cardiovascular diseases ,MACROPHAGES ,NEURON NAVIGATOR ,Original Research - 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. publishedVersion
- Published
- 2021