iScience (Mar 2022)
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
Affiliations
- Natali Froese
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
- Julio Cordero
- Department of Anatomy and Developmental Biology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany
- Aya Abouissa
- Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Ludolf-Krehl-Str. 7-11, 68167 Mannheim, Germany
- Felix A. Trogisch
- Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Ludolf-Krehl-Str. 7-11, 68167 Mannheim, Germany
- Steve Grein
- Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Ludolf-Krehl-Str. 7-11, 68167 Mannheim, Germany
- Malgorzata Szaroszyk
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
- Yong Wang
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
- Anna Gigina
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
- Mortimer Korf-Klingebiel
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
- Berislav Bosnjak
- Institute of Immunology, 30625 Hannover, Germany
- Colin F. Davenport
- Research Core Unit Genomics, Hannover Medical School, 30625 Hannover, Germany
- Lutz Wiehlmann
- Research Core Unit Genomics, Hannover Medical School, 30625 Hannover, Germany
- Robert Geffers
- Genome Analytics, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany
- Eva Riechert
- Department of Internal Medicine III, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
- Lonny Jürgensen
- Department of Internal Medicine III, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany
- Etienne Boileau
- Department of Internal Medicine III, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, 69120 Heidelberg, Germany
- Yanzhu Lin
- Department of Experimental Pharmacology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany
- Christoph Dieterich
- Department of Internal Medicine III, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, 69120 Heidelberg, Germany
- Reinhold Förster
- Institute of Immunology, 30625 Hannover, Germany
- Johann Bauersachs
- Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
- Roxana Ola
- Department of Experimental Pharmacology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany
- Gergana Dobreva
- Department of Anatomy and Developmental Biology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, 68167 Mannheim, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
- Mirko Völkers
- Department of Internal Medicine III, Medical Faculty of Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
- Joerg Heineke
- Department of Cardiovascular Physiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Ludolf-Krehl-Str. 7-11, 68167 Mannheim, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 3
p. 103965
Abstract
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.
