Key result
sST2 promotes cardiac fibrosis in viral myocarditis by inhibiting fibroblast senescence and activating TGF-β1 signaling.
Why the study?
The role of sST2 in regulating senescence and fibrosis in cardiac fibroblasts and its pathological role in viral myocarditis were unclear.
Does anti-ST2 mAb reduce cardiac fibrosis and modulate cellular senescence in mice with viral myocarditis?
Does anti-ST2 mAb reduce cardiac fibrosis and modulate cellular senescence in mice with viral myocarditis?
sST2 promotes cardiac fibrosis in viral myocarditis by inhibiting cardiac fibroblast senescence, a pathogenic process that can be reversed by anti-ST2 monoclonal antibodies.
Anti-ST2 mAb may attenuate fibrosis via senescence in murine viral myocarditis; hypothesis-generating and leaves open human translation.
Soluble interleukin 1 receptor-like 1 (sST2) is a novel predictor of poor outcomes, which is involved in inflammatory response and fibrosis of myocarditis. Cardiac fibrosis is a major cause of cardiovascular disease. Cellular senescence is a state of irreversible cell cycle arrest and studies have shown that senescence of myofibroblasts can limit or reduce myocardial fibrosis. Previous studies show that cellular senescence is associated with the progress of myocarditis, and cardiac fibroblasts is closely related to cardiac fibrosis. Therefore, we investigated the role of sST2 on senescence and fibrosis in mice cardiac fibroblasts (MCF). Meanwhile, its pathological role in mice viral myocarditis (VMC) was also investigated. In vitro experiments revealed that sST2 is beneficial to activate MCF by TGF-β1/Smad2/3 signaling and inhibit cell senescence by Sirt1/P53/P21 signaling pathway. CVB3-infected mice exhibited an increased deposition of collagen in the heart and decreased MCF senescence compared to WT mice while these pathological effects are reversed by anti-ST2 mAb. In addition, we found that inhibiting the senescence of MCF is beneficial to cardiac fibrosis and this effect is achieved by paracrine action. The present study reveals a new pathogenic pathway, sST2, which leads to cardiac fibrosis of VMC by inhibiting MCF senescence.
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Tan et al. (2022) studied Viral myocarditis and cardiac fibrosis. Anti-ST2 mAb / sST2 vs. Control / VMC without treatment was evaluated on Cardiac fibrosis and cellular senescence. sST2 promotes cardiac fibrosis in viral myocarditis by inhibiting cardiac fibroblast senescence through the Sirt1/p53/p21 signaling pathway and activating fibroblasts via TGF-β1/Smad2/3 signaling.
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