NYMC Faculty Publications
The AAV-PCSK9 Murine Model of Atherosclerosis and Metabolic Dysfunction
Author Type(s)
Faculty
DOI
10.1093/ehjopen/oeac028
Journal Title
European Heart Journal Open
First Page
oeac028
Document Type
Article
Publication Date
5-1-2022
Department
Medicine
Abstract
AIMS: Mouse models with genetic modifications are required to investigate atherogenesis and associated metabolic syndrome. Adeno-associated virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) induces hyperlipidaemia and promotes atherosclerosis in C57BL/6 mice. We aimed to assess whether AAV8-PCSK9-injected C57BL/6 mice fed high-fat diet with added cholesterol (HFD-C) would serve as a model of combined metabolic syndrome and atherosclerosis. METHODS AND RESULTS: C57BL/6 mice received i.v. injection of AAV-PCSK9 and sex- and age-matched and C57BL/6 control mice were placed on HFD-C or chow diet for 20 weeks (B6-PCSK9-HFD-C, HFD-C, B6-HFD-C, and B6-Chow, respectively). High-fat diet with added cholesterol feeding led to insulin resistance and impaired glucose clearance in B6-PCSK9-HFD-C mice compared with B6-Chow controls. This decrease in metabolic health in B6-PCSK9-HFD-C mice as well as the development of atherosclerosis was similar to HFD-C mice. Importantly, HFD-C feeding induced pancreatic islet hyperplasia in B6-PCSK9-HFD-C and B6-HFD-C compared with B6-Chow controls. In line with alterations in the metabolic phenotype, there was an increase in the number of pro-inflammatory Ly6C monocytes within the adipose tissues of B6-PCSK9-HFD-C and B6-HFD-C compared with B6-Chow controls. CONCLUSION: High-fat diet with added cholesterol-fed AAV-PCSK9-injected C57BL/6 mice can serve as a useful model of integrated metabolic syndrome and atherosclerosis that does not require genetic manipulations.
Recommended Citation
Keeter, W. C., Carter, N. M., Nadler, J. L., & Galkina, E. V. (2022). The AAV-PCSK9 Murine Model of Atherosclerosis and Metabolic Dysfunction. European Heart Journal Open, 2 (3), oeac028. https://doi.org/10.1093/ehjopen/oeac028