Macrophage pyroptosis is mediated by immunoproteasome subunit β5i (LMP7) in abdominal aortic aneurysm

Biochem Biophys Res Commun. 2020 Dec 17;533(4):1012-1020. doi: 10.1016/j.bbrc.2020.09.082. Epub 2020 Oct 2.

Abstract

Macrophages contribute to abdominal aortic aneurysm (AAA), but the effect of macrophage on AAA formation is not totally understood. Recent research proved that macrophage pyroptosis plays an important role in many cardiovascular disease. However, whether macrophage pyroptosis is involved in AAA and its mechanism remains unknown. In this study, we found that the pyroptosis significantly increased in AAA tissues. β5i inhibitor PR-957 treatment or β5i deficiency markedly ameliorated AAA formation and decreased the pyroptosis. Pyroptosis were also significantly attenuated in bone marrow derived macrophages (BMDM) from β5i-/- mice compared with the control group when they were subjected to OXLDL. Mechanistically, β5i may promote activation of NFκB which augment NLRP3 expression. In conclusion, this study suggested macrophages pyroptosis are involved in AAA and inhibition or knockout of β5i decreased macrophage pyroptosis via IκB/NFκB pathway.

Keywords: Abdominal aortic aneurysm; Macrophage; NLRP3,β5i; Pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal / drug therapy
  • Aortic Aneurysm, Abdominal / immunology*
  • Aortic Aneurysm, Abdominal / pathology*
  • Macrophages / immunology*
  • Macrophages / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Knockout, ApoE
  • NF-kappa B / metabolism
  • Oligopeptides / pharmacology
  • Proteasome Endopeptidase Complex / deficiency
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology*
  • Proteasome Inhibitors / pharmacology
  • Pyroptosis / drug effects
  • Pyroptosis / genetics
  • Pyroptosis / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • NF-kappa B
  • Oligopeptides
  • PR-957
  • Proteasome Inhibitors
  • RNA, Messenger
  • LMP7 protein
  • Proteasome Endopeptidase Complex