Aspirin reprograms platelet signaling and the intrahepatic microbiome to suppress RyR2-driven inflammation and fibrosis in preclinical chronic liver disease

overload, ER/mitochondrial stress (p < 0.05). Further, RyR2 blockade in HSCs reduced its activation by activated platelet secretome or TGFβ1 (p < 0.05). CONCLUSIONS: Platelet deactivation using aspirin regresses hepatic fibrosis by decreasing intrahepatic platelet accumulation/activation, inflammation and modulation of intrahepatic microbiome. Induction of RyR2 is critical for fibrosis development and pharmacological inhibition of RyR2 could ameliorate liver fibrosis.