1. Academic Validation
  2. Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway

Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway

  • Free Radic Biol Med. 2022 Mar;182:171-181. doi: 10.1016/j.freeradbiomed.2022.02.027.
Fenghong Wang 1 Qingqing Liang 2 Yuexiao Ma 2 Mengqi Sun 2 Tianyu Li 2 Lisen Lin 2 Zhiwei Sun 3 Junchao Duan 4
Affiliations

Affiliations

  • 1 Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China; Sinopharm North Hospital, Baotou, 014040, PR China.
  • 2 Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China.
  • 3 Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China. Electronic address: zwsun@ccmu.edu.cn.
  • 4 Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China. Electronic address: jcduan@ccmu.edu.cn.
Abstract

Growing literatures suggest that silica nanoparticles (SiNPs) exposure is correlated with adverse cardiovascular effects. Cardiac hypertrophy is one of the most common risk factors for heart failure. However, whether SiNPs involved in cardiac hypertrophy and the underlying mechanisms was remained unexploited. Our study aimed to investigate the molecular mechanisms of SiNPs on Pyroptosis and cardiac hypertrophy. The in vivo results found that SiNPs induced ultrastructural change and histopathological damage, accompanied by oxidative damage occurred and increased levels of inflammatory factors (IL-18 and IL-1β) in heart tissue. In addition, SiNPs could upregulate the expressions of cardiac hypertrophy-related special marker including ANP, BNP, β-MHC, it also elevated the pyroptosis-related protein, such as NLRP3, Cleaved-Caspase-1, GSDMD, IL-18 and Cleaved-IL-1β in vivo. For in vitro study, SiNPs increased the intracellular ROS generation and activated the NLRP3/Caspase-1/GSDMD signaling pathway in cardiomyocytes. Whereas, the NADPH Oxidase (NOX) inhibitor VAS2870 had effectively inhibited the ROS level and suppressed the expression of NLRP3, ASC, Pro-Caspase-1, Cleaved-Caspase-1, N-GSDMD, IL-18, Cleaved-IL-1β, ANP, BNP and β-MHC. Moreover, transfected with si-NLRP3 or adopted with Caspase-1 inhibitor VX-765 in cardiomyocytes showed an inhibitory effect on SiNPs-induced Pyroptosis and cardiac hypertrophy. In summary, our results demonstrated that SiNPs could trigger Pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 signaling pathway.

Keywords

Cardiac hypertrophy; Inflammation; Pyroptosis; ROS/NLRP3/Caspase-1 pathway; Silica nanoparticles.

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