Colchicine prevents disease progression in viral myocarditis via modulating the NLRP3 inflammasome in the cardiosplenic axis

Autor: Kathleen Pappritz, Jie Lin, Muhammad El‐Shafeey, Henry Fechner, Uwe Kühl, Alessio Alogna, Frank Spillmann, Ahmed Elsanhoury, Rainer Schulz, Carsten Tschöpe, Sophie Van Linthout
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: ESC Heart Failure, Vol 9, Iss 2, Pp 925-941 (2022)
Druh dokumentu: article
ISSN: 2055-5822
DOI: 10.1002/ehf2.13845
Popis: Abstract Aim The acute phase of a coxsackievirus 3 (CVB3)‐induced myocarditis involves direct toxic cardiac effects and the systemic activation of the immune system, including the cardiosplenic axis. Consequently, the nucleotide‐binding oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome pathway is activated, which plays a role in disease pathogenesis and progression. The anti‐inflammatory drug colchicine exerts its effects, in part, via reducing NLRP3 activity, and has been shown to improve several cardiac diseases, including acute coronary syndrome and pericarditis. The aim of the present study was to evaluate the potential of colchicine to improve experimental CVB3‐induced myocarditis. Methods and results C57BL6/j mice were intraperitoneally injected with 1 × 105 plaque forming units of CVB3. After 24 h, mice were treated with colchicine (5 μmol/kg body weight) or phosphate‐buffered saline (PBS) via oral gavage (p.o.). Seven days post infection, cardiac function was haemodynamically characterized via conductance catheter measurements. Blood, the left ventricle (LV) and spleen were harvested for subsequent analyses. In vitro experiments on LV‐derived fibroblasts (FB) and HL‐1 cells were performed to further evaluate the anti‐(fibro)inflammatory and anti‐apoptotic effects of colchicine via gene expression analysis, Sirius Red assay, and flow cytometry. CVB3 + colchicine mice displayed improved LV function compared with CVB3 + PBS mice, paralleled by a 4.7‐fold (P
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