Expression of a PCSK9 Gain-of-Function Mutation in C57BL/6J Mice to Facilitate Angiotensin II-Induced AAAs

Research output: Contribution to journalComment/debate

1 Scopus citations

Abstract

Angiotensin II (AngII) infusion in mice has been used widely to investigate mechanisms of abdominal aortic aneurysms (AAAs). To achieve a high incidence of AngII-induced AAAs, mice should be hypercholesterolemic. Therefore, either low-density lipoprotein receptor (LDLR) or apolipoprotein E deficiency have been used as a hypercholesterolemic background. However, it is a time-consuming and expensive process to generate compound deficient strains that have either an LDLR or apolipoprotein E deficient background. Proprotein convertase subtilisin/kexin type 9 (PCSK9) facilitates the degradation of LDL receptors. Previous studies demonstrated profound increases of plasma cholesterol concentrations after a single intraperitoneal injection of adeno-associated viruses (AAV) expressing a gain-of-function mutation of mouse PCSK9 (AAV.mPCSK9D377Y) in C57BL/6J mice fed a Western diet. Of note, injection of AAV.mPCSK9D377Y augmented AngII-induced AAA formation in C57BL/6J mice that had comparable severity of AAAs to LDLR deficient mice. Thus, AAV.mPCSK9D377Y infection greatly expedites studies on a gene of interest using AngII-induced AAAs. This commentary provides a brief technical guide of this approach and discusses the pros and cons of its use in AAA research.

Original languageEnglish
Article number915
JournalBiomolecules
Volume12
Issue number7
DOIs
StatePublished - Jul 2022

Bibliographical note

Funding Information:
Funding: The authors’ AAV.mPCSK9D377Y and aortic aneurysm-related research work is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL139748 and R35HL155649) and the American Heart Association SFRN in Vascular Disease (18SFRN33900001). The content in this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • PCSK9
  • adeno-associated virus
  • angiotensin
  • aortic aneurysm
  • hypercholesterolemia
  • mouse

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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