| First Author | Zhou T | Year | 2022 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1868 |
| Issue | 12 | Pages | 166497 |
| PubMed ID | 35868482 | Mgi Jnum | J:327144 |
| Mgi Id | MGI:7328258 | Doi | 10.1016/j.bbadis.2022.166497 |
| Citation | Zhou T, et al. (2022) GYY4137 ameliorates sepsis-induced cardiomyopathy via NLRP3 pathway. Biochim Biophys Acta Mol Basis Dis 1868(12):166497 |
| abstractText | Sepsis-induced cardiomyopathy (SICM) has a poor prognosis, with no effective therapeutic strategy currently. This study aimed to explore the mechanism underlying SICM and investigate the protective role of the hydrogen sulfide (H2S) donor GYY4137. This study included patients with SICM and animal models of SICM with wild-type and Nlrp3(-/-) mice, which were treated with or without GYY4137. Echocardiography, ELISA, TUNEL staining, and immunofluorescence were used to investigate phenotypic alterations. Serum levels of H2S and cytokines were measured. Inflammatory cell infiltration in the myocardial tissue was identified using immunohistochemistry and immunofluorescence. RNA expression profiles were identified using RNA sequencing. The protective mechanism of GYY4137 was further validated in the crosstalk between macrophages and cardiomyocytes using immunoblotting, real-time polymerase chain reaction (RT-PCR), and immunofluorescence when conditional medium of macrophages boosted by LPS were co-cultured with cardiomyocytes. Patients and animal models of SICM presented with lower serum H2S levels and heart dysfunction. GYY4137 reduced macrophage infiltration in septic heart tissue. GO analysis suggested that GYY4137 was involved in the inflammatory process. GYY4137 inhibited NLRP3 inflammasome activity in macrophages, reduced the secretion of inflammatory factors, and decreased the production of reactive oxygen species (ROS) in cardiomyocytes, thus exerting protective effects against SICM. We further found that the protective effects of GYY4137 were absent in Nlrp3-knockout models. GYY4137 ameliorates myocardial injury in SICM via the NLRP3 pathway by inhibiting the inflammatory response and reducing the production of myocardial ROS. |
