RESUMO
The NLR family pyrin domain containing 3 (NLRP3) inflammasome matures interleukin (IL)-1ß and induces inflammation. The molecular chaperone heat shock protein 90 (Hsp90) is known to regulate the formation of the NLRP3 inflammasome. However, the pathophysiological role of Hsp90 in the activation of the NLRP3 inflammasome in the failing heart is unclear. In the present study, we examined the pathophysiological role of Hsp90 in IL-1ß activation via inflammasomes using rats with heart failure following myocardial infarction in vivo and neonatal rat ventricular myocytes (NRVMs) in vitro. In the failing hearts, immunostained images showed an increase in NLRP3-positive spots. Increases in cleaved caspase-1 and mature IL-1ß levels were also observed. In contrast, treatment of the animals with an Hsp90 inhibitor reversed the increases in these values. In in vitro experiments, the activation of NLRP3 inflammasomes and the increase in mature IL-1ß induced by exposure of NRVMs to nigericin were attenuated by treatment with the Hsp90 inhibitor. Furthermore, coimmunoprecipitation assays indicated that the administration of an Hsp90 inhibitor to NRVMs attenuated the interaction between Hsp90 and its cochaperone SGT1. Our findings suggest that Hsp90 plays an important role in the regulation of NLRP3 inflammasome formation during the development of chronic heart failure after myocardial infarction in rats.