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P2×7 purinergic signaling in dilated cardiomyopathy induced by auto-immunity against muscarinic M2 receptors: autoantibody levels, heart functionality and cytokine expression
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, Scientific Reports
- Publication Year :
- 2015
-
Abstract
- Autoantibodies against the M2 receptors (M2AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2×7 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2×7−/− mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M2AChR cDNA sequence, WT mice produced anti-M2AChR antibodies, while P2×7−/− mice showed an attenuated production. Despite this, WT and P2×7−/− showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M2AChR WT immunized mice to näive recipients led to an alteration in heart shape. P2×7−/− mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3+CD25− subset. M2AChR WT immunized mice showed an increase in IL-1β, IFNγ and IL-17 levels in the heart, while P2×7−/− group produced lower amounts of IL-1β and IL-17 and higher amounts of IFNγ. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems and underscored the participation of IL-17 and IFNγ in the progress of autoimmune DCM.
- Subjects :
- Cardiomyopathy, Dilated
medicine.medical_specialty
Interleukin-1beta
Population
Cardiomyopathy
Autoantigens
T-Lymphocytes, Regulatory
Article
Interferon-gamma
Mice
Heart Rate
Physical Conditioning, Animal
Internal medicine
medicine
Animals
symbols.heraldic_charge
IL-2 receptor
education
Receptor
Ventricular remodeling
Autoantibodies
Mice, Knockout
Receptor, Muscarinic M2
education.field_of_study
Multidisciplinary
Ventricular Remodeling
business.industry
Myocardium
Interleukin-17
Heart shape
Interleukin-2 Receptor alpha Subunit
Autoantibody
Forkhead Transcription Factors
Dilated cardiomyopathy
medicine.disease
Mice, Inbred C57BL
Endocrinology
Gene Expression Regulation
Immunology
AUTOANTICORPOS
symbols
Female
Immunization
Receptors, Purinergic P2X7
business
Spleen
Plasmids
Signal Transduction
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, Scientific Reports
- Accession number :
- edsair.doi.dedup.....7186e8a47cb559557a106bd7b89cedea