HMGB1 producing by viable cardiac fibroblasts led to myocardial contractile dysfunction via PKC-β/Erk1/2/CBP Signal Pathway (174.21)

Abstract HMGB1 is a nuclear protein actively secreted by immune cells, cardiomyocyte, hepatocytes, pituicyte and passively released by necrotic cells. HMGB1 has been implicated in both lethality associated with endotoxemia/sepsis and cardiac contractile dysfunction. Therefore, the present work was to assess whether viable cardiac fibroblasts could release HMGB1 and whether HMGB1 could affect myocardial function. In vitro, cardiac fibroblasts were isolated and treated by LPS. HMGB1 mRNA showed no significant change during 0-12 h after stimulation with LPS, but increased significantly after 24h. Furthermore, the western blotting and immunofluorescence were also showed the same data. We found that HMGB1 active secretion might be PKC-β, Erk1/2, and CBP signal pathway. Meanwhile, we also found that collagen type I, III and osteopontin expression were increased after LPS stimulation. No evidence of inflammatory cells infiltration were noted in vivo. The type-B ultrasonic also showed that actively secreted HMGB1 by cardiac-fibroblast contributed to myocardial contractile dysfunction in sepsis. The findings of current study indicate that 1) LPS can induce HMGB1 secretion by viable cardiac fibroblasts may through PKC-β, Erk1/2, CBP signaling pathway, and 2) HMGB1 plays a role in LPS-induce myocardial contractile dysfunction. The results of the current study also have broader implications that might be more viable cells could secreted HMGB1.