Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20122 Milan, Italy.
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 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).
在心力衰竭中，异常铁稳态、心肌功能和预后之间的生物学和临床联系是已知的；然而，心肌组织和单细胞水平上与铁相关的基因的表达谱尚未得到很好的定义。通过公开的成人非衰竭 (NF) 和扩张型心肌病 (DCM) 受试者左心室样本的批量和单核 RNA 测序 (RNA-seq) 数据集，我们旨在评估整个心脏组织和单细胞水平上疾病状态下铁代谢的变化。从批量 RNA-seq 数据中，我们发现了 223 个在心肌组织水平上表达的与铁相关的基因，以及 44 个在 DCM 和 NF 受试者之间差异表达的基因。在单细胞水平上，与 NF 受试者相比，DCM 中的至少 18 个与铁相关的基因表达受到显著调节。具体而言，DCM 心肌细胞中的铁代谢在几个水平上发生改变，包括：(1)Fe 内化的不平衡（下调）和 Fe 向内转化为 Fe 的减少（下调），(2)产生血红蛋白的铁消耗增加（上调），(3)血红素合成和外化增加（上调），(4)血红素裂解为 Fe、胆红素和一氧化碳减少（下调），以及 (5)hepcidin 的正调控（上调）。
