Development of novel animal model for heart failure with a preserved ejection fraction

Heart failure (HF) is the commonest cardiovascular cause for hospital admission in people aged >65years. It has become increasingly evident that HF with preserved ejection fraction (HFpEF) is the commonest form of HF, accounting for more than 50% of all cases. Concerningly, to date, very few therapy has been shown to improve survival or to consistently reduce hospitalization and quality of life. As such, HFpEF remains an area of major unmet clinical need. The pathophysiology of HFpEF is complex driven by inflammation and fibrosis due to multiple comorbidities including aging, female sex, hypertension, obesity and diabetes. The lack of understanding of the complex pathophysiology involved in HFpEF impedes the development of effective therapy for the disease. To comprehensively explore the complex pathology fo HFpEF, a clinically relevant animal model is crucial. A good HFpEF animal model needs to feature obesity or over-weight, metabolic abnormality, inflammation, hypertension, cardiac fibrosis, and diastolic dysfunction that are consistent with the high prevalence of obese/overweight patients in human HFpEF disease. We will develop a novel HFpEF animal model in this study involving aging, female sex, hypertension, obesity, and diabetes leading to inflammation, cardiac remodelling with increased myocardial and arterial stiffness and diastolic dysfunction related to aging and concomitant hypertension. Project Aims: This project is aimed to develop and validate a novel animal model for heart failure with a preserved ejection fraction which can be used for the investigation of the pathophysiology involved in the development and progression of HFpEF. The model developed can also be used for the study of the therapeutic efficacy of new compounds to develop novel therapy for HFpEF. Techniques: It is anticipated that this study will involve the use of animal models in mice, cardiac function measurement with echocardiography and pressure-volume relationship analysis, Western blotting, immunohistochemistry, and gene expression analysis with PCR.