Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2887
• Main Authors: Massaiu, Ilaria, Campodonico, Jeness, Mapelli, Massimo, Salvioni, Elisabetta, Valerio, Vincenza, Moschetta, Donato, Myasoedova, Veronika A., Cappellini, Maria Domenica, Pompilio, Giulio, Poggio, Paolo, Agostoni, Piergiuseppe
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.02.2023; MDPI
• Subjects: 5-Aminolevulinate Synthetase - genetics; Adult; Antigens; Cardiomyocytes; Cardiomyopathy; Cardiomyopathy, Dilated - metabolism; Cardiovascular disease; Down-Regulation; Fibroblasts; Gene expression; Heart; Heart Failure - metabolism; Hemoglobin; Homeostasis; Humans; Iron; Metabolism; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Peptides; Physiology; Prostate; Proteins; Scavenger Receptors, Class A - genetics; heart failure; iron metabolism dysregulation; bulk RNA-seq; DEG analysis; snRNA-seq; DCM
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032887

In heart failure, the biological and clinical connection between abnormal iron homeostasis, myocardial function, and prognosis is known; however, the expression profiles of iron-linked genes both at myocardial tissue and single-cell level are not well defined. Through publicly available bulk and single-nucleus RNA sequencing (RNA-seq) datasets of left ventricle samples from adult non-failed (NF) and dilated cardiomyopathy (DCM) subjects, we aim to evaluate the altered iron metabolism in a diseased condition, at the whole cardiac tissue and single-cell level. From the bulk RNA-seq data, we found 223 iron-linked genes expressed at the myocardial tissue level and 44 differentially expressed between DCM and NF subjects. At the single-cell level, at least 18 iron-linked expressed genes were significantly regulated in DCM when compared to NF subjects. Specifically, the iron metabolism in DCM cardiomyocytes is altered at several levels, including: (1) imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation), (2) increase of iron consumption to produce hemoglobin (HBA1/2 up-regulation), (3) higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation), (4) lower cleavage of heme to Fe2+, biliverdin and carbon monoxide (HMOX2 down-regulation), and (5) positive regulation of hepcidin (BMP6 up-regulation).