Novel role for caspase 1 inhibitor VX765 in suppressing NLRP3 inflammasome assembly and atherosclerosis via promoting mitophagy and efferocytosis.

ABSTRACT: Atherosclerosis is a maladaptive chronic inflammatory disease, which remains the leading cause of death worldwide. The NLRP3 inflammasome constitutes a major driver of atherosclerosis, yet the mechanism of action is poorly understood. Mitochondrial dysfunction is essential for NLRP3 inflammasome activation. However, whether activated NLRP3 inflammasome exacerbates mitochondrial dysfunction remains to be further elucidated. Herein, we sought to address these issues applying VX765, a well-established inhibitor of caspase 1. VX765 robustly restrains caspase 1-mediated interleukin-1β production and gasdermin D processing. Our study assigned VX765 a novel role in antagonizing NLRP3 inflammasome assembly and activation. VX765 mitigates mitochondrial damage induced by activated NLRP3 inflammasome

SUBMITTER: Jin Y 

PROVIDER: S-EPMC9156694 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature