GSDMD Mediates LPS-Induced Septic Myocardial Dysfunction by Regulating ROS-dependent NLRP3 Inflammasome Activation

• DOI: 10.3389/fcell.2021.779432
• Publication Date: 2021-11-08T05:38:16Z
• Authors: Shanshan Dai; Bozhi Ye; Lingfeng Zhong; Yanghao Chen; Guangliang Hong; Guangju Zhao; Lan Su; Zhongqiu Lu
• Keywords: Creatine kinase

Myocardial dysfunction is a serious consequence of sepsis and contributes to high mortality. Currently, the molecular mechanism myocardial induced by remains unclear. In present study, we investigated role gasdermin D (GSDMD) in cardiac septic mice underlying mechanism. C57BL/6 wild-type (WT) age-matched Gsdmd-knockout (Gsdmd-/-) were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg) mimic sepsis. The results showed that GSDMD-NT, functional fragment GSDMD, was upregulated heart tissue WT LPS, which accompanied decreased function injury, as shown ejection fraction (EF) fractional shortening (FS) increased troponin I (cTnI), creatine kinase isoenzymes MB (CK-MB), lactate dehydrogenase (LDH). Gsdmd-/- exhibited protection against LPS-induced had higher survival rate. Gsdmd deficiency attenuated injury cell death. prevented increase interleukin-1β (IL-1β) tumor necrosis factor-α (TNF-α) serum, well IL-1β TNF-α mRNA levels myocardium. addition, LPS-mediated inflammatory infiltration into myocardium ameliorated activation NF-κB signaling pathway NOD-like receptor protein 3 (NLPR3) inflammasome suppressed mice. Further research mice, GSDMD-NT enrichment mitochondria led mitochondrial reactive oxygen species (ROS) overproduction, further regulated NLRP3 inflammasome. summary, our data suggest GSDMD plays vital pathophysiology may be crucial target for prevention treatment sepsis-induced dysfunction.