ABSTRACT
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.
Subject(s)
Arrhythmias, Cardiac/immunology , Cardiomyopathies/immunology , Desmoglein 2/metabolism , Fibrosis/physiopathology , Heart Failure/physiopathology , Inflammation/complications , Animals , Disease Models, Animal , Humans , Inflammation/pathology , MiceABSTRACT
Alcoholism remains one of the main causes of premature death in the population of Russia. Hence, the importance of the problem of uncontrolled distribution and consumption of surrogate alcoholic products, such as alcohol-containing liquids of uncertain origin. The objective of the present study was to detect ethyl alcohol, polyhexamethylene guanidine hydrochloride, and diethylphthalate in disinfectant liquids, biological fluids and human tissues and to analyse qualitative and quantitative composition of these materials.
