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Novel Model of Constrictive Pericarditis Associated With Autoimmune Heart Disease in Interferon-γ–Knockout Mice
Abstract
Background Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model. Methods and results Cardiac myosin-induced experimental autoimmune myocarditis in interferon (IFN)-gamma-knockout (KO) mice results in increased cardiac inflammation and development of severe grossly detectable pericarditis. Using in vivo pressure-volume studies, we found that the acute phase of experimental autoimmune myocarditis in IFN-gamma-KO mice was characterized by reduced left ventricular (LV) volumes compared with wild-type mice. The KO mice exhibited a classic restrictive/constrictive phenotype with decreased cardiac output, increased chamber stiffness, preserved ejection fraction, and impaired diastolic filling, characterized by reduced deceleration time and pressure tracings showing the square root sign similar to that observed in clinical cases of constrictive pericarditis. This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis. Comparison of IFN-gamma-KO and wild-type mice matched for the severity of myocardial disease further confirmed that pericarditis, and not myocarditis, was responsible for smaller LV volumes, reduced cardiac output, increased cardiac stiffness, and incre…
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IFNs reduce viral replication and prevent remodeling and fibrosis and thereby progression to DCM.
“However, IFNs reduce viral replication and prevent remodeling and fibrosis and thereby progression to DCM. 128,169,170”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [170]
Type I and II IFNs are a dominant immune response in CVB3 myocarditis models and EAM, where inhibition of these pathways leads to increased viral replication, pericardial and myocardial inflammation, and DCM.
“Type I and II IFNs are a dominant immune response in CVB3 myocarditis models (and EAM) where inhibition of these pathways leads to increased viral replication, pericardial and myocardial inflammation, and DCM. 124,128,152,169,170”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [170]
This time course is the same as observed with the autoimmune CVB3 and murine cytomegalovirus models of myocarditis and EAM.
“This time course is the same as is observed with the autoimmune CVB3 and murine cytomegalovirus models of myocarditis and EAM (Table S1). 35,124,170,188”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [170]
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Metadata
- Authors
- Afanasyeva, M., Georgakopoulos, D., Fairweather, D., Caturegli, P., Kass, D. A., & Rose, N. R.
- Affiliations
- Johns Hopkins University (US)
- ORCID
- Venue
- Circulation
- Published
- 2004-11-02
- Volume
- 110
- Issue
- 18
- Pages
- 2910-2917
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2138992780
- Cited by
- 42
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2020: 4 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2013: 1 · 2012: 7
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 67290, R01HL067290, HL 70729, R01HL070729)
- National Institute of Allergy and Infectious Diseases (AI 51835, R21AI051835)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Pericarditis and Cardiac Tamponade
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Keywords
- constrictive pericarditis, interferon-gamma knockout mice, experimental autoimmune myocarditis, cardiac myosin, autoimmune heart disease, pericardial inflammation, pericardial fibrosis, left ventricular stiffness, diastolic filling, cardiac output, animal models
- MeSH terms
- Animals, Autoimmune Diseases, Cardiac Output, Low, Diastole, Disease Models, Animal, Female, Fibrosis, Heart Ventricles, Interferon-gamma, Mice, Inbred BALB C, Myocarditis, Organ Size, Pericarditis, Constrictive, Phenotype, Pressure, Stroke Volume, Weight Loss, Mice, Knockout, Mice
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