Can NLRP3 (Nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3) inflammasome activation contribute to an elevated Coronary Artery Calcium (CAC) score?

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From the Research

NLRP3 Inflammasome Activation and Coronary Artery Calcium Score

  • The activation of the NLRP3 inflammasome has been associated with various inflammatory diseases, including coronary artery disease 1, 2.
  • A study published in 2020 found that the NLRP3 polymorphism rs10159239 was significantly associated with a higher coronary calcium score in a cohort of Vietnam War veterans 1.
  • The NLRP3 inflammasome is activated by various stimuli, including pathogens and danger-associated molecular patterns, and plays a critical role in the innate immune response 3, 4.
  • The activation of the NLRP3 inflammasome leads to the secretion of proinflammatory cytokines, such as IL-1β and IL-18, and pyroptotic cell death 5, 3.
  • Elevated plasma NLRP3 inflammasome levels have been correlated with disease severity and poorer short-term outcomes in patients with acute coronary syndrome 2.

Mechanism of NLRP3 Inflammasome Activation

  • The leucine-rich repeat (LRR) domain of NLRP3 is required for NLRP3 inflammasome activation in macrophages 5.
  • The endoplasmic reticulum (ER) plays a critical role in NLRP3 inflammasome activation, providing a location for NLRP3 activation and association with ligands released from or residing in mitochondria 3.
  • ER-stress signaling and lipid perturbation also contribute to NLRP3 inflammasome activation 3.

Association with Coronary Artery Calcium Score

  • The NLRP3 polymorphism rs10159239 has been associated with a higher coronary calcium score, suggesting a potential link between NLRP3 inflammasome activation and coronary artery disease 1.
  • Elevated plasma NLRP3 inflammasome levels have been correlated with disease severity and poorer short-term outcomes in patients with acute coronary syndrome, further supporting the association between NLRP3 inflammasome activation and coronary artery disease 2.

References

4
Research

The NLRP3-Inflammasome in Health and Disease.

International journal of molecular sciences, 2022

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