Header

UZH-Logo

Maintenance Infos

Cardiomyopathy in murine models of systemic sclerosis


Abstract

Objectives. Cardiomyopathy has emerged as a leading cause of death in systemic sclerosis (SSc). However, the pathogenesis of SSc-related cardiomyopathy is poorly understood and new therapies as well as platforms for testing are needed. Here, we aimed to characterize the histopathological features of cardiomyopathy in SSc patients and in common mouse models of SSc. Methods. The histopathological features in myocardial tissues of five patients with SSc and five controls matched for sex, age and cardiovascular risk factors were evaluated and compared to those of three common mouse models of SSc with systemic manifestations: Fra-2 transgenic (Fra-2 tg) mice, mice with sclerodermatous chronic Graft versus Host disease (cGvHD) and tight skin 1 (Tsk-1) mice. Results: Myocardial tissues of SSc patients without clinically manifest cardiac involvement showed endothelial cell apoptosis with reduced capillary density, perivascular inflammation, myofibroblast differentiation and accumulation of collagen. The cGvHD and Tsk-1 models displayed only selected features of SSc-related cardiomyopathy. However, myocardial tissue of Fra-2 tg mice mimicked all features of SSc-related cardiomyopathy and also demonstrated comparable vascular, inflammatory and fibrotic manifestations. Of note, the expression of Fra-2 was also increased in the myocardium of SSc patients. Conclusions. We demonstrate that all typical manifestations of SSc-related cardiomyopathy are mimicked by Fra-2 tg mice. Moreover, the overexpression of Fra-2 in the myocardium of SSc patients may suggest similar underlying pathomechanisms. Thus, Fra-2 tg mice might be a suitable preclinical model to study the mechanisms and therapeutic approaches of myocardial involvement in SSc. \ © 2014 American College of Rheumatology.

Abstract

Objectives. Cardiomyopathy has emerged as a leading cause of death in systemic sclerosis (SSc). However, the pathogenesis of SSc-related cardiomyopathy is poorly understood and new therapies as well as platforms for testing are needed. Here, we aimed to characterize the histopathological features of cardiomyopathy in SSc patients and in common mouse models of SSc. Methods. The histopathological features in myocardial tissues of five patients with SSc and five controls matched for sex, age and cardiovascular risk factors were evaluated and compared to those of three common mouse models of SSc with systemic manifestations: Fra-2 transgenic (Fra-2 tg) mice, mice with sclerodermatous chronic Graft versus Host disease (cGvHD) and tight skin 1 (Tsk-1) mice. Results: Myocardial tissues of SSc patients without clinically manifest cardiac involvement showed endothelial cell apoptosis with reduced capillary density, perivascular inflammation, myofibroblast differentiation and accumulation of collagen. The cGvHD and Tsk-1 models displayed only selected features of SSc-related cardiomyopathy. However, myocardial tissue of Fra-2 tg mice mimicked all features of SSc-related cardiomyopathy and also demonstrated comparable vascular, inflammatory and fibrotic manifestations. Of note, the expression of Fra-2 was also increased in the myocardium of SSc patients. Conclusions. We demonstrate that all typical manifestations of SSc-related cardiomyopathy are mimicked by Fra-2 tg mice. Moreover, the overexpression of Fra-2 in the myocardium of SSc patients may suggest similar underlying pathomechanisms. Thus, Fra-2 tg mice might be a suitable preclinical model to study the mechanisms and therapeutic approaches of myocardial involvement in SSc. \ © 2014 American College of Rheumatology.

Statistics

Citations

5 citations in Web of Science®
3 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:27 Feb 2015 09:30
Last Modified:13 May 2016 10:25
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:2326-5205
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/art.38942
PubMed ID:25371068

Download

Full text not available from this repository.
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations