Myocardial Expression of the Anaphylatoxin Receptor C3aR is Associated with Cardiac Inflammation and Prognosis in Patients with Non-Ischaemic Heart Failure
Open accessAbstract
Aim: The aim of this study is to analyse the prognostic value of complement anaphylatoxin receptors in patients with non-ischaemic cardiomyopathy undergoing endomyocardial biopsy. Methods and results: In 102 patients (72.5% male patients, median age 54 years) with non-ischaemic cardiomyopathy, myocardial expression of C3aR was assessed among other parameters. The primary study endpoint was a composite of death, heart transplantation, heart failure-related re-hospitalization, and deterioration of left ventricular ejection fraction within a mean follow-up of 11.9 months. The number of cells, which stained positive for C3aR, was significantly increased in patients with inflammatory compared with non-inflammatory cardiomyopathy (1.75 ± 0.31 cells in inflammatory cardiomyopathy vs. 0.94 ± 0.26 in non-inflammatory cardiomyopathy, P = 0.049). Subsequently, positive expression for C3aR was judged based on a semi-quantitative scoring system. Significantly, more patients with positive MHCII and CD68 expression showed an increased number of C3aR-positive cells. C3aR expression based on this score was more pronounced in patients with human herpesvirus 6 viral genome detection. Kaplan–Meier curves illustrate that the C3aR-negative group reached the primary endpoint significantly more often (mean follow-up 11.9 months, log rank 5.963, P = 0.015). Lack of C3aR expression was a strong independent predictor for the primary endpoint in Cox regression analysis [hazard ratio 0.46 (0.26–0.82, P = 0.009)]. Conclusions: C3aR-positive cells are found more often in patients with inflammatory cardiomyopathy. The relevance of C3aR-positive cells in patients with non-ischaemic cardiomyopathy should be further evaluated as potential predictors or modulators of adverse cardiac remodelling, the substrate of progressive heart failure.
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Mast cells work in cooperation with macrophages to increase profibrotic inflammation and remodeling that leads to scar and DCM.
“Mast cells work in cooperation with macrophages to increase profibrotic inflammation and remodeling that leads to scar and DCM (Figure 4). 129,157,158,160”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [158]
The Introduction (page unavailable) links sustained immune activation and inflammatory-cell infiltration to myocardial fibrosis and cardiac remodelling. The Results (page unavailable) find more macrophages in inflammatory cardiomyopathy, and the Introduction mentions mast-cell degranulation. Neither passage says mast cells cooperate with macrophages to cause profibrotic inflammation, scarring, or DCM. (LLM, conf=0.82)
Experimental — accuracy not yet measuredMast cells and macrophages work together to drive inflammation and fibrosis.
“Mast cells and macrophages work together to drive inflammation and fibrosis. 129,158”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [158]
The Introduction links prolonged myocardial inflammation to fibrosis and describes mast-cell degranulation and macrophage infiltration in inflammatory pathways. The Results also find more macrophages in inflammatory cardiomyopathy. Neither section shows that mast cells and macrophages work together to drive inflammation and fibrosis. (LLM, conf=0.84)
Experimental — accuracy not yet measuredElevated expression of C3aR and CD68+ macrophages was found in patients with myocarditis compared with those with cardiomyopathy without inflammation.
“Elevated expression of C3aR (and CD68+ macrophages) was found in patients with myocarditis compared with those with cardiomyopathy without inflammation. 158”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [158]
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Self-citation
- Authors
- Mueller, K. A. L., Patzelt, J., Sauter, M., Maier, P., Gekeler, S., Klingel, K., Kandolf, R., Seizer, P., Gawaz, M., Geisler, T., & Langer, H. F.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Geisler, Tobias
- Langer, Harald F.
- ORCID
- Venue
- ESC Heart Failure
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-08-31
- Volume
- 5
- Issue
- 5
- Pages
- 846-857
- ISSN
- 2055-5822 (ISSN-L)
- PMC
- PMC6165948
- OpenAlex
- W2889103118
- Cited by
- 12
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ESC Heart Failure (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- TÜFF Frauenförderungsprogramm of the University Tübingen (2241-0-0)
- Deutsche Forschungsgemeinschaft (KFO 274)
- Volkswagen Foundation (Lichtenberg program)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- C3a receptor, anaphylatoxins, non-ischemic heart failure, non-ischemic cardiomyopathy, myocarditis, prognostic factors, endomyocardial biopsy, human herpesvirus 6, MHC class II, CD68+ macrophages, cardiac remodeling, heart failure readmission
- MeSH terms
- Adult, Aged, Aged, 80 and over, Biopsy, Echocardiography, Female, Follow-Up Studies, Gene Expression Regulation, Heart Failure, Humans, Immunohistochemistry, Male, Middle Aged, Myocardium, Prognosis, Receptors, Complement, Retrospective Studies, RNA, Young Adult
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