Tangzhiqing Exacerbates Oxidized Low-Density Lipoprotein-Induced Cell Pyroptosis Through Activation of NLRP3 Inflammasome in Human Umbilical Vein Endothelial Cells.

Abstract

Atherosclerosis (AS) is a chronic and progressive inflammatory condition affecting arterial walls. It is widely accepted that the deposition of low-density lipoprotein (LDL) and its adverse impact on endothelial cells (ECs) play a pivotal role in the development of AS. Specifically, oxidized LDL (ox-LDL) has been validated as a trigger for inducing pyroptosis in ECs, thereby contributing significantly to intima inflammation and AS progression. However, the underlying molecular mechanisms require further investigation. In this study, we demonstrated that ox-LDL significantly upregulates the expression of pyrin domain-containing 3 (NLRP3) protein levels in ECs. This upregulation is associated with increased caspase-1 cleavage, interleukin-1β (IL-1β) maturation, and lactate dehydrogenase (LDH) release. Moreover, ox-LDL also upregulates the expression of ASC, caspase-1, GSDMD, IL-1β, and IL-18 proteins. The inhibition of NLRP3-specific inhibitor MCC950 or caspase-1-specific inhibitor VX-765 effectively suppressed the expression of cellular pyroptosis-associated proteins. Our findings highlight the crucial role of Tangzhi Qing (TZQ) in regulating ox-LDL-induced pyroptosis and inflammation through the activation of the NLRP3 inflammasome. This suggests that NLRP3 inflammasome could serve as a promising therapeutic target for mitigating diseases associated with atherosclerosis.