@article{3165714,
    title = "Complement system modulation as a target for treatment of arrhythmogenic
cardiomyopathy",
    author = "Mavroidis, Manolis and Davos, Constantinos H. and Psarras, Stelios and and Varela, Aimilia and Athanasiadis, Nikolaos C. and Katsimpoulas, Michalis and and Kostavasili, Ioanna and Maasch, Christian and Vater, Axel and van and Tintelen, J. Peter and Capetanaki, Yassemi",
    journal = "Basic Research in Cardiology",
    year = "2015",
    volume = "110",
    number = "3",
    publisher = "Springer Berlin Heidelberg",
    issn = "0300-8428, 1435-1803",
    doi = "10.1007/s00395-015-0485-6",
    keywords = "Arrhythmias; Myocardial inflammation; Innate immunity; Genetic models;
Cytoskeleton",
    abstract = "Inflammation may contribute to disease progression in arrhythmogenic
cardiomyopathy (ACM). However, its role in this process is unresolved.
Our goal was to delineate the pathogenic role of the complement system
in a new animal model of ACM and in human disease. Using cardiac
histology, echocardiography, and electrocardiography, we have
demonstrated that the desmin-null mouse (Des-/-) recapitulates most of
the pathognomonic features of human ACM. Massive complement activation
was observed in the Des-/- myocardium in areas of necrotic cells debris
and inflammatory infiltrate. Analysis of C5aR-/-Des-/- double-null
animals and a pharmaceutical approach using a C5a inhibitor were used to
delineate the pathogenic role of the complement system in the disease
progression. Our findings indicate that inhibiting C5aR (CD88) signaling
improves cardiac function, histopathology, arrhythmias, and survival
after endurance. Containment of the inflammatory reaction at the
initiation of cardiac tissue injury (2-3 weeks of age), with
consequently reduced myocardial remodeling and the absence of a direct
long-lasting detrimental effect of C5a-C5aR signaling on cardiomyocytes,
could explain the beneficial action of C5aR ablation in Des-/-
cardiomyopathy. We extend the relevance of these findings to human
pathophysiology by showing for the first time significant complement
activation in the cardiac tissues of patients with ACM, thus suggesting
that complement modulation could be a new therapeutic target for ACM."
}