Long-term exposure to silica nanoparticles induces cardiac hypertrophy through the pyroptosis pathway.

While acute cardiovascular effects of silicon nanoparticles (SiNPs) have been reported, the long-term impact of human-relevant exposure on cardiac hypertrophy remains unclear. The rats were randomly assigned to two groups: The SiNPs exposure group and the control group, receiving intratracheal instillations of SiNPs suspension or saline, respectively, once a week for six months (24 doses total). Both groups then underwent a six-month recovery period without further intervention to assess post-exposure effects. The results revealed significant hypertrophic remodeling, as evidenced by increased left ventricular anterior wall thickness (LVAWd), systolic dysfunction (reduced FS%), and diastolic impairment (prolonged LVRT and LVCT). Ultrastructural analysis indicated mitochondrial disorganization and swelling in myocardial tissue. At the molecular level, SiNPs exposure upregulated hypertrophic markers (β-MHC, ANP), inflammatory cytokines (IL-18, IL-1β), and oxidative stress markers MDA, while reducing SOD levels. Both classical (Caspase-1) and non-classical (Caspase-4, Caspase-5) pyroptosis pathways were activated, with elevated levels of Cleaved-Caspase-1, ASC and N-GSDMD. This study is the first to identify non-classical pyroptosis as a contributor to SiNPs-induced cardiac hypertrophy. Importantly, cardiac hypertrophy was significantly reduced after exposure cessation, with no further pyroptosis-mediated inflammatory damage observed. These findings underscore the importance of stricter public health regulations to limit SiNPs exposure, given its long-term cardiovascular risks.

• Publication year

  2025

• Venue

  Toxicological Sciences

• Publication date

  2025-04-26

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1093/toxsci/kfaf046PMID 40286312
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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