Lentivirus-mediated RNA interference of chymase increases the plaque stability in atherosclerosis in vivo

Exp Mol Pathol. 2013 Aug;95(1):51-6. doi: 10.1016/j.yexmp.2013.05.005. Epub 2013 May 24.

Abstract

Chymase activity was proved to be closely related with plaque vulnerability in a hamster model of atherosclerosis with chymase inhibitors. Considering that chymase inhibitors are nonspecific, here we further investigated the role of chymase in atherosclerosis in vivo through injection of lentivirus containing chymase shRNA or chymase cDNA. Our results revealed that silencing of the chymase gene by shRNA remarkably enhanced atherosclerosis plaque stability without alterations in body weight or serum lipid levels. Lentiviral expression of a gain-of-function chymase gene promoted the formation of vulnerable plaque in hamsters. Mechanistically, chymase functions as an activator of MMP9 in atherosclerotic lesions that induces plaque instability.

Keywords: Atherosclerosis; Chymase; Matrix metalloproteinase 9; RNA interference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / enzymology*
  • Atherosclerosis / pathology*
  • Chymases / genetics*
  • Chymases / metabolism
  • Cricetinae
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic
  • Lentivirus / genetics*
  • Lipids / blood
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Plaque, Atherosclerotic / enzymology*
  • Plaque, Atherosclerotic / pathology
  • Plaque, Atherosclerotic / virology
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Lipids
  • RNA, Small Interfering
  • Chymases
  • Matrix Metalloproteinase 9