Cardiac fibroblast sub-types in vitro reflect pathological cardiac remodeling in vivo
Open accessAbstract
Many heart diseases are associated with fibrosis, but it is unclear whether different types of heart disease correlate with different subtypes of activated fibroblasts and to which extent such diversity is modeled during in vitro activation of primary cardiac fibroblasts. Analyzing the expression of 82 fibrosis related genes in 65 heart failure (HF) patients, we identified a panel of 12 genes clearly distinguishing HF patients better from healthy controls than measurement of the collagen-related hydroxyproline content. A subcluster enriched in ischemic HF was recognized, but not for diabetes, high BMI, or gender. Single-cell transcriptomic analysis of in vitro activated mouse cardiac fibroblasts distinguished 6 subpopulations, including a contractile Acta2high precursor population, which was predicted by time trajectory analysis to develop into Acta2low subpopulations with high production of extracellular matrix molecules. The 12 gene profile identified in HF patients showed highest similarity to the fibroblast subset with the strongest expression of extracellular matrix molecules. Population markers identified were furthermore able to clearly cluster different disease stages in a murine model for myocardial infarct. These data suggest that major features of cardiac fibroblast activation in heart failure patients, in murine heart disease models, and in cell culture of primary murine cardiac fibroblast are shared.
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Fibroblasts are of particular interest in cardiac disease given their role in tissue fibrosis, arrhythmias, and heart failure.
“Among stromal cell types, fibroblasts are of particular interest given their role in tissue fibrosis, arrhythmias, and heart failure 16,29,30 .”
From Targeting the Immune-Fibrosis Axis in Myocardial Infarction and Heart Failure (2022) · cites this paper as [16]
The Introduction links cardiac fibroblasts to fibrosis and describes a strong correlation between fibrosis and heart failure; the Discussion also discusses targeting matrix-producing fibroblasts to treat fibrosis. No passage found in our copy addresses a role for fibroblasts in arrhythmias, so that part of the attributed claim is unsupported. Page numbers were not available in the copy. (LLM, conf=0.86)
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Targeting immune–fibroblast cell communication in heart failure
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- Authors
- Herum, K. M., Weng, G., Kahnert, K., Waikel, R., Milburn, G., Conger, A., Anaya, P., Campbell, K. S., Lundby, A., Won, K. J., & Brakebusch, C.
- Affiliations
- University of Copenhagen (DK)
- University of Kentucky (US)
- Corresponding author
- Brakebusch, Cord
- ORCID
- Venue
- Matrix Biology Plus
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 15
- Pages
- 100113
- ISSN
- 2590-0285 (ISSN-L)
- PMC
- PMC9198323
- OpenAlex
- W4281667355
- Cited by
- 15
- References
- 26
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2022: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Matrix Biology Plus (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novo Nordisk Fonden (NNF17CC0027852)
- University of Kentucky
- Danmarks Frie Forskningsfond (DFF-0199-00001B)
- Horizon 2020 Framework Programme
- H2020 Marie Skłodowska-Curie Actions
- Independent Research Fund Denmark (0135-00243B)
- Horizon 2020
- Europäische Kommission (795390)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- cardiac fibroblasts, fibroblast heterogeneity, cardiac remodeling, heart failure, fibrosis, fibroblast activation, ACTA2, extracellular matrix, single-cell transcriptomics, myocardial infarction, gene expression signatures, hydroxyproline
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