Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure

• Published in: Scientific reports Vol. 14; no. 1; p. 5811
• Main Authors: Frisk, Christoffer, Das, Sarbashis, Eriksson, Maria J., Walentinsson, Anna, Corbascio, Matthias, Hage, Camilla, Kumar, Chanchal, Ekström, Mattias, Maret, Eva, Persson, Hans, Linde, Cecilia, Persson, Bengt
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/1647/2017; 692/4019; Actin; Apoptosis; Biopsy; Cardiac biopsy; Cardiac muscle; Congestive heart failure; Cytoskeleton; Echocardiography; Gene expression; Gene Expression Profiling; Heart failure; Heart Failure - diagnosis; Heart Failure - genetics; Heart Ventricles; Humanities and Social Sciences; Humans; Ion channels (cyclic nucleotide-gated); Ischemic heart disease; Left ventricular dysfunction; Medicin och hälsovetenskap; multidisciplinary; Muscle contraction; Peptides; Phenotypes; Principal components analysis; Science; Science (multidisciplinary); Smooth muscle; Stat4 protein; Stroke Volume - physiology; Transcription factors; Transcriptomics; Ventricle; Ventricular Dysfunction, Left; Ventricular Function, Left; β-Catenin; Heart failure; Ischemic heart disease; Cardiac biopsy; Left ventricular dysfunction; Gene expression
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-56025-1

New or mild heart failure (HF) is mainly caused by left ventricular dysfunction. We hypothesised that gene expression differ between the left (LV) and right ventricle (RV) and secondly by type of LV dysfunction. We compared gene expression through myocardial biopsies from LV and RV of patients undergoing elective coronary bypass surgery (CABG). Patients were categorised based on LV ejection fraction (EF), diastolic function and NT-proBNP into pEF (preserved; LVEF ≥ 45%), rEF (reduced; LVEF < 45%) or normal LV function. Principal component analysis of gene expression displayed two clusters corresponding to LV and RV. Up-regulated genes in LV included natriuretic peptides NPPA and NPPB, transcription factors/coactivators STAT4 and VGLL2, ion channel related HCN2 and LRRC38 associated with cardiac muscle contraction, cytoskeleton, and cellular component movement. Patients with pEF phenotype versus normal differed in gene expression predominantly in LV, supporting that diastolic dysfunction and structural changes reflect early LV disease in pEF. DKK2 was overexpressed in LV of HFpEF phenotype, potentially leading to lower expression levels of β-catenin, α-SMA (smooth muscle actin), and enhanced apoptosis, and could be a possible factor in the development of HFpEF. CXCL14 was down-regulated in both pEF and rEF, and may play a role to promote development of HF.