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

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; Joerg Heineke

doi:10.1016/j.isci.2022.103965

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

iScience. 2022 Feb 23;25(3):103965. doi: 10.1016/j.isci.2022.103965. eCollection 2022 Mar 18.

Authors

Natali Froese¹, Julio Cordero², Aya Abouissa³, Felix A Trogisch³, Steve Grein³, Malgorzata Szaroszyk¹, Yong Wang¹, Anna Gigina¹, Mortimer Korf-Klingebiel¹, Berislav Bosnjak⁴, Colin F Davenport⁵, Lutz Wiehlmann⁵, Robert Geffers⁶, Eva Riechert⁷, Lonny Jürgensen⁷, Etienne Boileau^{7

8

9}, Yanzhu Lin¹⁰, Christoph Dieterich^{7

8

9}, Reinhold Förster⁴, Johann Bauersachs¹, Roxana Ola¹⁰, Gergana Dobreva^{2

8}, Mirko Völkers^{7

8}, Joerg Heineke^{3

8}

Affiliations

¹ Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany.
² Department of Anatomy and Developmental Biology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany.
³ Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Ludolf-Krehl-Str. 7-11, 68167 Mannheim, Germany.
⁴ Institute of Immunology, 30625 Hannover, Germany.
⁵ Research Core Unit Genomics, Hannover Medical School, 30625 Hannover, Germany.
⁶ Genome Analytics, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
⁷ Department of Internal Medicine III, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany.
⁸ German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
⁹ Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, 69120 Heidelberg, Germany.
¹⁰ Department of Experimental Pharmacology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany.

Abstract

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.

Keywords: Biological sciences; Molecular biology; Systems biology; Transcriptomics.