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

Int J Mol Sci. 2023 Feb 2;24(3):2887. 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).

Keywords: DCM; DEG analysis; bulk RNA-seq; heart failure; iron metabolism dysregulation; snRNA-seq.

MeSH terms

  • 5-Aminolevulinate Synthetase / genetics
  • Adult
  • Cardiomyopathy, Dilated* / metabolism
  • Down-Regulation
  • Heart Failure* / metabolism
  • Humans
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism
  • Scavenger Receptors, Class A / genetics


  • ALAS2 protein, human
  • 5-Aminolevulinate Synthetase
  • SCARA5 protein, human
  • Scavenger Receptors, Class A