Early inflammation precedes cardiac fibrosis and heart failure in desmoglein 2 murine model of arrhythmogenic cardiomyopathy
| Autor: | N. Zaman, S.L.M. Walker, Keat-Eng Ng, Joseph Westaby, G. Mastroianni, Ryan C. Pink, S. Murtough, Paul J. Delaney, D. Thenet, Elena Tsisanova, Daniel J. Pennington, C.M. Webb, Andrew Tinker, David P. Kelsell |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Histology Desmoglein 2 (Dsg2) Cardiac fibrosis Cardiomyopathy Desmoglein-2 Cardiac inflammation and macrophages Inflammation 030204 cardiovascular system & hematology Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine Desmosome Fibrosis medicine Animals Humans Heart Failure Desmoglein 2 business.industry Arrhythmogenic cardiomyopathy (AC) Arrhythmias Cardiac Regular Article Cell Biology medicine.disease Disease Models Animal 030104 developmental biology medicine.anatomical_structure Heart failure Tumor necrosis factor alpha medicine.symptom Cardiomyopathies business |
| Zdroj: | Cell and Tissue Research |
| ISSN: | 1432-0878 |
| Popis: | The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in Dsg2-null (Dsg2−/−) hearts at postnatal day 14 (2 weeks) that were absent in the fibrotic heart of adult mice (10 weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression. |
| Databáze: | OpenAIRE |
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