Inflammation shapes pathogenesis of murine arrhythmogenic cardiomyopathy.

Basic Research in Cardiology
Nadine LubosClaudia A Krusche

Abstract

Arrhythmogenic cardiomyopathy (AC) is an incurable genetic disease, whose pathogenesis is poorly understood. AC is characterized by arrhythmia, fibrosis, and cardiodilation that may lead to sudden cardiac death or heart failure. To elucidate AC pathogenesis and to design possible treatment strategies of AC, multiple murine models have been established. Among them, mice carrying desmoglein 2 mutations are particularly valuable given the identification of desmoglein 2 mutations in human AC and the detection of desmoglein 2 auto-antibodies in AC patients. Using two mouse strains producing either a mutant desmoglein 2 or lacking desmoglein 2 in cardiomyocytes, we test the hypothesis that inflammation is a major component of disease pathogenesis. We show that multifocal cardiomyocyte necrosis initiates a neutrophil-dominated inflammatory response, which also involves macrophages and T cells. Increased expression of Ccl2/Ccr2, Ccl3/Ccr5, and Cxcl5/Cxcr2 mRNA reflects the observed immune cell recruitment. During the ensuing acute disease phase, Mmp12+ and Spp1+ macrophages and T cells accumulate in scars, which mature from cell- to collagen-rich. The expression of Cx3cl1/Cx3cr1, Ccl2/Ccr2, and Cxcl10/Cxcr3 dominates this disease phase...Continue Reading

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Citations

Dec 19, 2020·Chronic Diseases and Translational Medicine·Hui Wang, Zhi-Cheng Jing
Nov 17, 2020·Current Opinion in Physiology·Ruoshui Li, Nikolaos G Frangogiannis
Jun 6, 2021·Basic Research in Cardiology·Yen-Nien LinEugenio Cingolani
Aug 4, 2021·Chinese Medical Journal·Zhong-Yu YuanYong-Quan Wu
Sep 4, 2021·Current Heart Failure Reports·Brenda Gerull, Andreas Brodehl

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Methods Mentioned

BETA
transgenic
dissection
PCR
Assay

Software Mentioned

GraphPad Prism
LightCycler
GraphPad

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