<p>Endothelial cell (EC) injury is highly significant in both health toxicology and cardiovascular disease. In the context of environmental and occupational health, ECs are frequently the frontline responders to pathogens and toxicants. Upon exposure to such agents, endothelial dysfunction ensues, triggering a cascade of cellular fates including pyroptosis, apoptosis, and necroptosis, which together constitute PANoptosis. The NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome is a sentinel of cellular stress and is activated in response to environmental pollutants and chemical toxins. Notably, strategies aimed at suppressing NLRP3 activation, such as the potential deployment of specific antidotes or detoxifying agents, have shown promise in impeding endothelial injury and halting the progression of cardiovascular diseases (CVDs). In this review, we summarize the role of NLRP3 in endothelial injury, highlight its PANoptosis ramifications, and partially discuss its relationship with vascular toxicity, which may aid in the prevention and treatment of vascular disorders and toxicology.</p>

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NLRP3-Mediated PANoptosis and Associated Interventions in Endothelial Injury

  • Aiwei Yan,
  • Ting Cao,
  • Xiao Li,
  • Xingchen Li,
  • Chaochu Cui,
  • Xianwei Wang

摘要

Endothelial cell (EC) injury is highly significant in both health toxicology and cardiovascular disease. In the context of environmental and occupational health, ECs are frequently the frontline responders to pathogens and toxicants. Upon exposure to such agents, endothelial dysfunction ensues, triggering a cascade of cellular fates including pyroptosis, apoptosis, and necroptosis, which together constitute PANoptosis. The NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome is a sentinel of cellular stress and is activated in response to environmental pollutants and chemical toxins. Notably, strategies aimed at suppressing NLRP3 activation, such as the potential deployment of specific antidotes or detoxifying agents, have shown promise in impeding endothelial injury and halting the progression of cardiovascular diseases (CVDs). In this review, we summarize the role of NLRP3 in endothelial injury, highlight its PANoptosis ramifications, and partially discuss its relationship with vascular toxicity, which may aid in the prevention and treatment of vascular disorders and toxicology.