Related Experiment Video
Updated: Sep 2, 2025
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
The AAV-PCSK9 murine model of atherosclerosis and metabolic dysfunction
William Coles Keeter1, Nigeste M Carter2, Jerry L Nadler3
1Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Rd, LH3180, Norfolk 23507, VA, USA.
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 Ldlr and C57BL/6 control mice were placed on HFD-C or chow diet for 20 weeks (B6-PCSK9-HFD-C, Ldlr 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 Ldlr 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 Ly6Chigh/med 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.
