Oxidized low density lipoprotein induced caspase-1 mediated pyroptotic cell death in macrophages: implication in lesion instability?

PLoS One. 2013 Apr 25;8(4):e62148. doi: 10.1371/journal.pone.0062148. Print 2013.

Abstract

Background: Macrophage death in advanced lesion has been confirmed to play an important role in plaque instability. However, the mechanism underlying lesion macrophage death still remains largely unknown.

Methods and results: Immunohistochemistry showed that caspase-1 activated in advanced lesion and co-located with macrophages and TUNEL positive reaction. In in-vitro experiments showed that ox-LDL induced caspase-1 activation and this activation was required for ox-LDL induced macrophages lysis, IL-1β and IL-18 production as well as DNA fragmentation. Mechanism experiments showed that CD36 and NLRP3/caspase-1/pathway involved in ox-LDL induced macrophage pyroptosis.

Conclusion: Our study here identified a novel cell death, pyroptosis in ox-LDL induced human macrophage, which may be implicated in lesion macrophages death and play an important role in lesion instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CARD Signaling Adaptor Proteins
  • CD36 Antigens / metabolism
  • Carrier Proteins / metabolism
  • Caspase 1 / metabolism*
  • Cell Death / drug effects
  • Cytoskeletal Proteins / metabolism
  • DNA Fragmentation / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • Interleukin-18 / biosynthesis
  • Interleukin-1beta / biosynthesis
  • Lipoproteins, LDL / pharmacology*
  • Macrophages / cytology*
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Macrophages / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / immunology*
  • Plaque, Atherosclerotic / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • CARD Signaling Adaptor Proteins
  • CD36 Antigens
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Interleukin-18
  • Interleukin-1beta
  • Lipoproteins, LDL
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • PYCARD protein, human
  • Reactive Oxygen Species
  • oxidized low density lipoprotein
  • Caspase 1

Grants and funding

This work was supported by National Natural Science Foundation of China to Dr. Dazhu Li (NO. 81170258). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.