A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction

Our research aims at examining heart failure with preserved ejection fraction, known as HFpEF, specifically investigating the effects of lipotoxicity. We seek to elucidate the intricate relationship between metabolic syndrome and lipotoxicity in driving HFpEF progression and uncover the underlying mechanisms driving HFpEF pathophysiology using this experimental murine model. Despite the rising prevalence and limited treatment options for HFpEF, its pathophysiological mechanisms mainly related to metabolic syndrome remain poorly understood.

This model presents a unique opportunity to bridge this gap and potentially develop new therapies for HFpEF. Our model's most important advantage is its ability to mimic significant lipid mishandling observed in HFpEF patients. This mouse model offers valuable insights into the pathophysiology of HFpEF, especially cardiac metabolism.

Our findings underscore the importance of fatty acid and cholesterol mishandling in cardiometabolic HFpEF. This model perfectly shows how fatty acid deprivation disrupts metabolism at different levels. It provides researchers with potential avenues to discover novel traps for HFpEF patients.

Here at the Shahada Laboratory, we will focus on translating this model into large animals. We will investigate questions related to the pathogenesis, sudden death, and potential therapeutic interventions targeting lipotoxicity, inflammation, and cardiac remodeling.