Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy.
International journal of molecular sciences(2023)
摘要
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 Fe internalization ( down-regulation) and reduction of internal conversion from Fe to Fe ( down-regulation), (2) increase of iron consumption to produce hemoglobin ( up-regulation), (3) higher heme synthesis and externalization ( and up-regulation), (4) lower cleavage of heme to Fe, biliverdin and carbon monoxide ( down-regulation), and (5) positive regulation of hepcidin ( up-regulation).
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关键词
DCM,DEG analysis,bulk RNA-seq,heart failure,iron metabolism dysregulation,snRNA-seq
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