Mimicking Metabolic Disturbance in Establishing Animal Models of Heart Failure With Preserved Ejection Fraction

Abstract

Heart failure (HF), the terminal state of different heart diseases, imposed a significant health care burden worldwide. It is the last battlefield in dealing with cardiovascular diseases. HF with preserved ejection fraction (HFpEF) is a type of HF in which the symptoms and signs of HF are mainly ascribed to diastolic dysfunction of left ventricle, whereas systolic function is normal or near-normal. Compared to HF with reduced ejection fraction (HFrEF), the diagnosis and treatment of HFpEF have made limited progress, partly due to the lack of suitable animal models for translational studies in the past. Given metabolic disturbance and inflammatory burden contribute to HFpEF pathogenesis, recent years have witnessed emerging studies focusing on construction of animal models with HFpEF phenotype by mimicking metabolic disorders. These models prefer to recapitulate the metabolic disorders and endothelial dysfunction, leading to the more detailed understanding of the entity. In this review, we summarize the currently available animal models of HFpEF with metabolic disorders, as well as their advantages and disadvantages as tools for translational studies.

Exercise training and experimental myocardial ischemia and reperfusion: A systematic review and meta-analysis

“…The ejection fraction indicates the amount of blood being ejected by the heart and the improvement of this index is an important indicator of the heart's recovery. ejection fraction is an important indicator both in animals and in clinical studies [46] , [47] , [48] .…”

HFpEF as systemic disease, insight from a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in HFpEF patients

“…Currently, systemic inflammation-induced microvascular endothelial dysfunction is deemed as one of the major contributors for the pathogenesis and progression of HFpEF 11 , 12 . Clusters of inflammation proteins were reported to mediate the coupling of comorbidity burden, right ventricular dysfunction and poor outcomes of HFpEF by increasing cardiomyocyte passive tension and aggravating aberrant myocardial collagen deposition 13 , 14 .…”

Understanding How Heart Metabolic Derangement Shows Differential Stage Specificity for Heart Failure with Preserved and Reduced Ejection Fraction

“…Although we recognize this limitation, we believe they might be effective in understanding more about the metabolic changes associated with HF. In reality, whereas HF slowly progresses in humans, HF-induced animal models minimize disease latency and may not result in the activation of the same molecular pathways, and hence biomarkers, along with bias due to reproducibility issues across various studies [ 11 ]. Another source of biological variability for HFpEF is the number of comorbidities in human illness, which is not considered in animal models.…”