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

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 deficienc...

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Published inBiomolecules (Basel, Switzerland) Vol. 12; no. 7; p. 915
Main Authors Sawada, Hisashi, Daugherty, Alan, Lu, Hong S.
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 29.06.2022
MDPI
Subjects
Abdomen
adeno-associated virus
Angiotensin
Angiotensin II
aortic aneurysm
Aortic aneurysms
Apolipoprotein E
Apolipoproteins
Atherosclerosis
Cholesterol
hypercholesterolemia
Infections
Injection
Kexin
Low density lipoprotein
Low density lipoprotein receptors
mouse
Mutation
PCSK9
Plasma
Proprotein convertases
Receptor density
Review boards
Rodents
Subtilisin
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Summary: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.
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ISSN:2218-273X
2218-273X
DOI:10.3390/biom12070915