Intravenous injection of PCSK9 gain-of-function mutation in C57BL/6J background mice on Angiotensin II-induced AAA

Objective: This study was performed to compare the incidence of Angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) between intravenous and intraperitoneal injection of AAV8.mPCSK9^D377Y in wild-type (WT) mice with C57BL/6J background and the pathological differences of above model in WT and ApoE^-/- mice.

Design: Male WT mice were injected intraperitoneally or intravenously with either a AAV8.null or AAV8.mPCSK9^D377Y. Two weeks after injection, all WT mice were infused with Ang II, and simultaneously age-matched male ApoE^-/- mice were infused with saline or Ang II for 4 weeks.

Results: Compared with intraperitoneal injection of AAV8.mPCSK9^D377Y for AAA model in WT mice, a higher incidence of Ang II-induced AAA, increased blood pressure (BP) and lipid concentration, lower collagen deposition and up-regulated inflammation response were shown by intravenous injection, which was similar to ApoE^-/- mice infused with Ang II.

Conclusion: AAV8.mPCSK9^D377Y infected male WT mice intravenously facilitate a high incident and comparable severity of Ang II-induced AAA which could be greatly expedites AAA studies on a gene of interest.