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Several mechanisms in the fibrotic transformation of synovial fibroblast into myofibroblasts have been identified including the TLR engagement, NLRP3 inflammasome activation, pro-inflammatory cytokines (e.g., TNF-, IL-1), growth factors (e.g., TGF-, CTGF), metabolic reprogramming (characterized by succinate accumulation, enhanced glycolysis, and glutaminolysis), hypoxia-induced HIF activation, and mitochondrial dysfunction leading to ROS generation and the SASP
Importantly, there was an apparent improvement in cardiac function in the cAtg3-KO mice following treatment [8]