(733.13) Role of stress granule activation in cardiomyocyte function in sepsis

Poster Board Number: E280

Yaqiao Wang (Jiangsu University, Jiangsu University), Kehan Wu (Jiangsu University), Runmin Liu (Jiangsu University), Hao Wang (Jiangsu University), Tao Rui (Jiangsu University, Lawson Health Research Institution)

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is the leading cause of mortality in Intensive Care Unit (ICU). Sepsis-induced myocardial dysfunction (SIMD) is a major complication of the sepsis that contributes to high mortality of patients with sepsis. Stress granule (SG) is a cytoplasmic membraneless platform that is formed in response to cellular stresses. The role of SG in SIMD is unknown. The aim of present study is to understand whether activation of SG in cardiomyocytes (CM) plays a role in CM function in sepsis.

Methods: CMs were treated with lipopolysaccharide (LPS). CM SG activation (eIF2α phosphorylation) and TNFα production were assessed with Western blot and ELISA, respectively. CM function was evaluated with intracellular cAMP. ISRIB or over-expression of G3BP1 was employed interfering SG.

Results: Challenging CMs with LPS results in eIF2α phosphorylation, an increase in TNFα production, and a decrease in intracellular cAMP in response to dobutamine. Pharmacologically (ISRIB) or genetically inhibition (G3BP1 knock down) of SG leads to an exaggerated increase in TNFα expression. Further, SG inhibition results in enhanced decrease in CM function (decreased intracellular cAMP) in CM with LPS. Over-expression of G3BP1 in CMs prevents LPS-induced CM TNFα production and improves CM contractility. 

Conclusion: Our results indicate that the cardiomyocyte stress granule activation plays a protective role of myocardial function in sepsis.

The study was supported by National Natural Science Foundation of China (82172172)