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A Preclinical Rat Model of Heart Failure With Preserved Ejection Fraction With Multiple Comorbidities
Géraldine Hubesch1, Aliénor Hanthazi1, Angela Acheampong1,2
1Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Frontiers in Cardiovascular Medicine
|January 31, 2022
Summary
Metabolic syndrome induced by a high-fat diet in rats caused heart failure with preserved ejection fraction (HFpEF). This preclinical model shows HFpEF development linked to metabolic dysfunction and cardiac remodeling.
Area of Science:
- Cardiology
- Metabolic Diseases
- Physiology
Background:
- Heart failure with preserved ejection fraction (HFpEF) lacks effective therapies.
- HFpEF frequently co-occurs with metabolic syndrome comorbidities.
- Metabolic syndrome's role in HFpEF pathogenesis is under investigation.
Purpose of the Study:
- To investigate if metabolic syndrome leads to diastolic dysfunction and HFpEF.
- To develop a preclinical HFpEF model with comorbidities.
- To evaluate pathobiological changes in diet-induced HFpEF.
Main Methods:
- Obesity-prone rats fed a high-fat diet (HFD) vs. controls on standard chow.
- Phenotyping metabolic syndrome, echocardiography, and cardiac hemodynamics at 4 and 12 months.
- Myocardial tissue and blood analysis including RNA-sequencing.
Main Results:
- HFD induced metabolic syndrome (obesity, glucose intolerance, hyperlipidemia) in rats.
- Associated findings included diastolic dysfunction, pulmonary hypertension, and preserved ejection fraction.
- Cardiac remodeling involved hypertrophy, fibrosis, and altered gene expression in fatty acid metabolism and calcium handling.
Conclusions:
- A 12-month HFD in susceptible rats creates a relevant preclinical HFpEF model.
- This model mimics HFpEF with comorbidities, suitable for testing new treatments.
- Metabolic syndrome is a key factor in HFpEF development and progression.
