Clinical Phenotypes of Heart Failure With Preserved Ejection Fraction to Select Preclinical Animal Models

Ham, Willem B. van; Kessler, Elise L.; Oerlemans, Marish I.F.J.; Handoko, M. Louis; Sluijter, Joost P.G.; Veen, Toon A.B. van; Ruijter, Hester M. den; Jager, Saskia C.A. de

doi:10.1016/j.jacbts.2021.12.009

Cited by 17 publications

(14 citation statements)

References 149 publications

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“…Our study has found that the LVEF index of the rats in model group was in line with the reported criteria for the HFpEF animal model ( van Ham et al, 2022 ). Plenty of studies have investigated the characteristics of the same rat model in terms of physiological parameters, such as LVEF ( Cho et al, 2018 ; Liu et al, 2021 ; Zhang et al, 2020 ) and they have provided powerful evidence for the efficient construction of HFpEF rat model in the present study.…”

Section: Discussionsupporting

confidence: 88%

Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology

Gao

Liu

et al. 2023

PeerJ

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Objective Heart failure with preserved ejection fraction (HFpEF) is a public health problem worldwide. Treatments for the patients with HFpEF are not satisfactory because there is no unified understanding of the pathological mechanism of HFpEF. This study aims at investigating the potential pathological mechanism for the effective diagnosis and treatment of HFpEF. Methods Ten adult male Dahl salt sensitive rats (180–200 g) were divided into control and model groups. The rats in model group were fed with high salt diet (8% NaCl) to induce HFpEF for this comparative study. Behavioral changes, biochemical parameters, and histopathological changes of the rats were detected. iTRAQ technology combined with bioinformatics analysis was employed to study the differentially expressed proteins (DEPs) and their enrichment in signaling pathways. Results Echocardiography detection showed decreased LVEF, indicating impaired cardiac function (P < 0.01), increased LVPWd, indicating ventricular wall hypertrophy (P < 0.05), prolonged duration of IVRT and decreased E/A ratio, indicating diastolic dysfunction (P < 0.05) of the rats in model group. 563 DEPs were identified in the rats of both groups, with 243 up-regulated and 320 down-regulated. The expression of PPAR signaling pathway in the rats of model group was down-regulated, with PPARα most significantly decreased (91.2%) (P < 0.01), PPARγ obviously decreased (63.60%) (P < 0.05), and PPARβ/δ decreased (45.33%) (P < 0.05). The DEPs enriched in PPAR signaling pathway were mainly related to such biological processes as fatty acid beta-oxidation, such cellular components as peroxisome, and such molecular functions as lipid binding. Conclusions NaCl high salt diet is one of the factors to increase the incidence of HFpEF in rats. PPARα, PPARγ and PPAR β/δ might be the targets of HFpEF. The findings may provide a theoretical basis for the treatment of HFpEF in clinical practice.

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Section: Discussionsupporting

confidence: 88%

Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology

Gao

Liu

et al. 2023

PeerJ

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“…However, a major drawback is the HFpEF definition. Many studies define disease outcomes based on structural and functional parameters, and the models actually represent extended LVDD models [ 149 ]. To overcome this, signs of congestion, such as lung weight, natriuretic peptide levels, and, ultimately, symptoms, should be taken into account.…”

Section: Mainmentioning

confidence: 99%

“…Over time, there has been a transition from simple single-hit models to multi-hit models involving age, a Western high fat/high sugar diet, diabetes, hypertension, hypercholesterolemia, and kidney dysfunction as stressors and/or comorbidities [148]. These models enable sex-specific and phenotype-specific research [148,149]. However, a major drawback is the HFpEF definition.…”

Section: Pre-clinical Researchmentioning

confidence: 99%

Diastolic dysfunction and sex-specific progression to HFpEF: current gaps in knowledge and future directions

Ommen

Canto

Rutten

et al. 2022

BMC Med

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Diastolic dysfunction of the left ventricle (LVDD) is equally common in elderly women and men. LVDD is a condition that can remain latent for a long time but is also held responsible for elevated left ventricular filling pressures and high pulmonary pressures that may result in (exercise-induced) shortness of breath. This symptom is the hallmark of heart failure with preserved ejection fraction (HFpEF) which is predominantly found in women as compared to men within the HF spectrum. Given the mechanistic role of LVDD in the development of HFpEF, we review risk factors and mechanisms that may be responsible for this sex-specific progression of LVDD towards HFpEF from an epidemiological point-of-view and propose future research directions.

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“…This is in contrast to the latest breakthrough advances in treating HF with reduced ejection fraction (HFrEF) ( 9 ). Importantly, developing new therapies for HFpEF has been slow in part because of the absence of a reliable animal model ( 10 ). In this review, we highlight the progress to date in identifying an optimal large animal model for preclinical studies of HFpEF treatments.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of large animal models for preclinical studies of heart failure with preserved ejection fraction using clinical score systems

Li¹,

Cardoso²,

Moctezuma-Ramirez³

et al. 2023

Front. Cardiovasc. Med.

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Heart failure with preserved ejection fraction (HFpEF) is characterized by a complex, heterogeneous spectrum of pathologic features combined with average left ventricular volume and diastolic dysfunction. HFpEF is a significant public health problem associated with high morbidity and mortality rates. Currently, effective treatments for HFpEF represent the greatest unmet need in cardiovascular medicine. A lack of an efficient preclinical model has hampered the development of new devices and medications for HFpEF. Because large animal models have similar physiologic traits as humans and appropriate organ sizes, they are the best option for limiting practical constraints. HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach. Here, we review the large animal models of HFpEF reported to date and describe the methods that have been used to create HFpEF, including surgery-induced pressure overloading, medicine-induced pressure overloading, and diet-induced metabolic syndrome. In addition, for the first time to our knowledge, we use two established clinical HFpEF algorithms (HFA-PEFF and H2FPEF scores) to evaluate the currently available large animal models. We also discuss new technologies, such as continuous remote pressure monitors and inflatable aortic cuffs, as well as how the models could be improved. Based on current progress and our own experience, we believe an efficient large animal model of HFpEF should simultaneously encompass multiple pathophysiologic factors, along with multiorgan dysfunction. This could be fully evaluated through available methods (imaging, blood work). Although many models have been studied, only a few studies completely meet clinical score standards. Therefore, it is critical to address the deficiencies of each model and incorporate novel techniques to establish a more reliable model, which will help facilitate the understanding of HFpEF mechanisms and the development of a treatment.

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Clinical Phenotypes of Heart Failure With Preserved Ejection Fraction to Select Preclinical Animal Models

Cited by 17 publications

References 149 publications

Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology

Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology

Diastolic dysfunction and sex-specific progression to HFpEF: current gaps in knowledge and future directions

Evaluation of large animal models for preclinical studies of heart failure with preserved ejection fraction using clinical score systems

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