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Analysis of myocardial cellular gene expression during pressure overload reveals matrix based functional intercellular communication

To identify cellular mechanisms responsible for pressure overload triggered heart failure, we isolated cardiomyocytes, endothelial cells, and fibroblasts as most abundant cell types from mouse hearts in the subacute and chronic stages after transverse aortic constriction (TAC) and performed RNA-sequ...

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Main Authors: Froese, Natali (Author) , Cordero, Julio (Author) , Abouissa, Aya (Author) , Trogisch, Felix (Author) , Grein, Steve (Author) , Szaroszyk, Malgorzata (Author) , Wang, Yong (Author) , Gigina, Anna (Author) , Korf-Klingebiel, Mortimer (Author) , Bosnjak, Berislav (Author) , Davenport, Colin F. (Author) , Wiehlmann, Lutz (Author) , Geffers, Robert (Author) , Riechert, Eva (Author) , Jürgensen, Lonny (Author) , Boileau, Etienne (Author) , Lin, Yanzhu (Author) , Dieterich, Christoph (Author) , Förster, Reinhold (Author) , Bauersachs, Johann (Author) , Ola, Roxana (Author) , Dobreva, Gergana (Author) , Völkers, Mirko (Author) , Heineke, Jörg (Author)
Format: Article (Journal)
Language:English
Published: March 18, 2022
In: iScience
Year: 2022, Volume: 25, Issue: 3, Pages: 1-29
ISSN:2589-0042
DOI:10.1016/j.isci.2022.103965
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.isci.2022.103965
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004222002358
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Author Notes:Natali Froese, Julio Cordero, Aya Abouissa, Felix A. Trogisch, Steve Grein, Malgorzata Szaroszyk, Yong Wang, Anna Gigina, Mortimer Korf-Klingebiel, Berislav Bosnjak, Colin F. Davenport, Lutz Wiehlmann, Robert Geffers, Eva Riechert, Lonny Jürgensen, Etienne Boileau, Yanzhu Lin, Christoph Dieterich, Reinhold Förster, Johann Bauersachs, Roxana Ola, Gergana Dobreva, Mirko Völkers, and Joerg Heineke
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Summary:To identify cellular mechanisms responsible for pressure overload triggered heart failure, we isolated cardiomyocytes, endothelial cells, and fibroblasts as most abundant cell types from mouse hearts in the subacute and chronic stages after transverse aortic constriction (TAC) and performed RNA-sequencing. We detected highly cell-type specific transcriptional responses with characteristic time courses and active intercellular communication. Cardiomyocytes after TAC exerted an early and sustained upregulation of inflammatory and matrix genes and a concomitant suppression of metabolic and ion channel genes. Fibroblasts, in contrast, showed transient early upregulation of inflammatory and matrix genes and downregulation of angiogenesis genes, but sustained induction of cell cycle and ion channel genes during TAC. Endothelial cells transiently induced cell cycle and extracellular matrix genes early after TAC, but exerted a long-lasting upregulation of inflammatory genes. As we found that matrix production by multiple cell types triggers pathological cellular responses, it might serve as a future therapeutic target.
Item Description:Gesehen am 01.04.2022
Physical Description:Online Resource
ISSN:2589-0042
DOI:10.1016/j.isci.2022.103965

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