Pathogenic Role of the Damage-Associated Molecular Patterns S100A8 and S100A9 in Coxsackievirus B3–Induced Myocarditis

• DOI: 10.1161/circheartfailure.117.004125
• Publication Date: 2017-11-21T01:10:40Z
• Authors: Irene Müller; Thomas Vogl; Kathleen Pappritz; Kapka Miteva; Konstantinos Savv...; David Rohde; Patrick Most; Dirk Lassner; Burkert Pieske; Uwe Kühl; Sophie Van Linthout; Carsten Tschöpe
• Keywords: S100A9; S100A8; Viral Myocarditis; Knockout mouse

Background: The alarmins S100A8 and S100A9 are damage-associated molecular patterns, which play a pivotal role in cardiovascular diseases, inflammation, viral infections. We aimed to investigate their Coxsackievirus B3 (CVB3)–induced myocarditis. Methods Results: mRNA expression was 13.0-fold ( P =0.012) 5.1-fold =0.038) higher endomyocardial biopsies from patients with CVB3-positive myocarditis compared controls, respectively. Elimination of CVB3 led downregulation these alarmins. CVB3-infected mice developed an impaired left ventricular function displayed increased protein versus controls. In contrast, knockout mice, also complete for on level, showed improved function, associated reduced cardiac inflammatory oxidative response, lower copy number wild-type mice. Exogenous application induced severe similar HL-1 cells, enhanced stress unstimulated infected cells. RAW macrophages, both MIP-2 (macrophage protein-2) chemokine expression, knockdown scrambled siRNA Conclusions: aggravate CVB3-induced might serve as therapeutic targets cardiomyopathies.