Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy
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Data di Pubblicazione:
2023
Citazione:
Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy / I. Massaiu, J.S. Campodonico, M. Mapelli, E. Salvioni, V. Valerio, D. Moschetta, V.A. Myasoedova, M.D. Cappellini, G. Pompilio, P. Poggio, P. Agostoni. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:3(2023 Feb 02), pp. 2887.1-2887.14. [10.3390/ijms24032887]
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Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy
by Ilaria Massaiu
1,†, Jeness Campodonico
1,†, Massimo Mapelli
1 [ORCID] , Elisabetta Salvioni
1, Vincenza Valerio
1, Donato Moschetta
1,2 [ORCID] , Veronika A. Myasoedova
1 [ORCID] , Maria Domenica Cappellini
3,4 [ORCID] , Giulio Pompilio
1,5, Paolo Poggio
1,*,‡ [ORCID] and Piergiuseppe Agostoni
1,4,*,‡
1
Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy
2
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20122 Milan, Italy
3
UOC General Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
4
Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
5
Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
*
Authors to whom correspondence should be addressed.
†
These authors equally contributed as first author.
‡
These authors equally contributed as last author.
Int. J. Mol. Sci. 2023, 24(3), 2887; https://doi.org/10.3390/ijms24032887
Received: 23 December 2022 / Revised: 19 January 2023 / Accepted: 26 January 2023 / Published: 2 February 2023
(This article belongs to the Special Issue Iron Metabolism in Health and Disease)
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Abstract
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).
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
iron metabolism dysregulation; DCM; heart failure; bulk RNA-seq; snRNA-seq; DEG analysis
Elenco autori:
I. Massaiu, J.S. Campodonico, M. Mapelli, E. Salvioni, V. Valerio, D. Moschetta, V.A. Myasoedova, M.D. Cappellini, G. Pompilio, P. Poggio, P. Agostoni
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