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

• Downregulation of chymase enhances the plaque stability in hamster model of atherosclerosis.
• Overexpression of chymase promotes the formation of vulnerable plaque in hamsters.
• Chymase functions as an activator of MMP9 to induce plaque instability.

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.