Endothelial Dysfunction in Vascular Inflammation: The Role of NLRP3, NLRP10, AIM2, TLR9, and PANoptosis

Diana L Silva-Velasco1,2, Rinaldo R Dos Passos3,4, Raiana Anjos Moraes3,4

  • 1Cardiovascular Translational Research Center, University of South Carolina, Columbia, SC, USA. diana.silvavelasco@uscmed.sc.edu.

Insights

Inflammasomes like NLRP3 and AIM2 contribute to vascular inflammation and endothelial dysfunction by releasing inflammatory cytokines. Targeting these pathways may offer new treatments for cardiovascular diseases.

Area of Science:

  • Cardiovascular Biology
  • Innate Immunity
  • Molecular Medicine

Background:

  • Endothelial dysfunction is central to vascular inflammation and cardiovascular diseases.
  • Inflammasome factors critically influence inflammatory and cell death pathways impacting endothelial homeostasis.

Purpose of the Study:

  • To elucidate the role of specific inflammasome sensors (NLRP3, AIM2, TLR9, NLRP10) in endothelial dysfunction.
  • To understand how these sensors mediate inflammatory responses and cell death, including PANoptosis.
  • To explore potential therapeutic targets for vascular dysfunction.

Main Methods:

  • Analysis of inflammasome activation pathways in endothelial cells.
  • Investigation of cytokine release (IL-1β, IL-18) and inflammatory signaling.
  • Examination of cell death mechanisms (pyroptosis, apoptosis, necroptosis, PANoptosis).

Main Results:

  • NLRP3 and AIM2 inflammasomes promote IL-1β and IL-18 release, amplifying vascular inflammation.
  • TLR9 activation by mitochondrial DNA enhances endothelial inflammatory cytokine secretion.
  • NLRP10 modulates inflammasome activity and NF-κB signaling.
  • Convergent signaling leads to pyroptosis, apoptosis, necroptosis, and PANoptosis, causing endothelial injury.

Conclusions:

  • Inflammasome pathways are key drivers of endothelial dysfunction and vascular inflammation.
  • These innate immune sensors integrate multiple cell death pathways, exacerbating endothelial injury.
  • Understanding these mechanisms provides novel therapeutic avenues for cardiovascular diseases.

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