Efficacy of a High Fat Diet and L-NAME Combinatory Mouse Model for Heart Failure With Preserved Ejection Fraction

Maggie Peng

Document Type

Article

Publication Date

Summer 2022

Keywords

JMG

JAX Location

In: Student Reports, Summer 2022, The Jackson Laboratory

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a subtype of heart failure with a complex phenotype including various risk factors and comorbidities including obesity and cardiac hypertrophy. Treatments for HFpEF are limited, partially due to the lack of working mouse models that fully recapitulate the range of HFpEF characteristics. Schiattarella et al. published a combinatory mouse model utilizing a 60% high fat diet (HFD) and N-nitro-L- arginine methyl ester (L-NAME), but their results have not yet been reproduced. The aim of this study was to successfully recapitulate the Schiattarella et al. model in C57BL/6NJ, used in the original study, and C57BL/6J mice, which have a mutated Nnt gene. Mice from each strain were divided into chow, HFD, L-NAME, and HFD + L-NAME groups. After 5 weeks of treatment, blood glucose tests, transthoracic echocardiography with strain analysis, and heart, lung, and tibia harvests were performed. C57BL/6NJ mice demonstrated a partial HFpEF phenotype with increased global longitudinal strain values and elevated blood glucose but lack of cardiac hypertrophy and lung congestion. C57BL/6J displayed no characteristics of HFpEF. The HFD + L-NAME model may be viable, but a longer treatment period is likely necessary for a more robust HFpEF phenotype.

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