Conclusion
FOXO1 overexpression attenuated apoptosis, ROS generation, and inflammation, whereas FOXO1 inhibition aggravated LPS-induced cardiomyocyte injury via the NLRP3 inflammasome signaling pathway.
Methods
Rat-derived H9c2 cells were subjected to LPS, and the manipulation of FOXO1 was achieved through overexpression and knockdown using the adeno-associated virus system and siRNA, respectively. Western blotting and quantitative real-time polymerase chain reaction were utilized to examine the inhibitory effect of FOXO1. Cell viability was examined utilizing Cell Counting Kit-8 assay. The changes of apoptosis were examined utilizing Annexin V-FITC/PI method. The levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-18, and tumor necrosis factor-α in the H9c2 cells were measured using ELISA kits. Reactive oxygen species (ROS) generation was quantified using the 2'-7'dichlorofluorescin diacetate assay kit.
Objective
Forkhead box protein O1 (FOXO1) has been shown to regulate multiple proteins in various cardiovascular disease processes. However, the effect of FOXO1 on lipopolysaccharide (LPS)-induced cardiotoxicity remains unknown. The aim of this study was to explore the impact of FOXO1 on LPS-induced cardiotoxicity.
Results
In H9c2 cells treated with LPS, FOXO1 expression was downregulated in a dose-dependent and time-dependent manner. Overexpression of FOXO1 attenuated LPS-induced apoptosis, oxidative stress injury, and cardiomyocyte inflammation, while FOXO1 inhibition aggravated these processes. Additionally, FOXO1 was found to regulate LPS-related myocardial injury by downregulating the expression of NLR family pyrin domain-containing 3 (NLRP3).