Review Article

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery

Si Gao1, Xue-ping Liu1, Ting-ting Li1, Li Chen1, Yi-ping Feng1, Yu-kun Wang1, Yan-jun Yin2, Peter J. Little3, Xiao-qian Wu4, Suo-wen Xu5, Xu-dong Jiang1
1 Department of Pharmacy, School of Medicine, Guangxi University of Science and Technology, Liuzhou 545005, China
2 School of Pharmacy, Bengbu Medical College, Bengbu 233000, China
3 School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, QLD 4102, Australia
4 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
5 Department of Endocrinology, First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Correspondence to: Xiao-qian Wu: wuxiaoqian@gzhmu.edu.cn, Suo-wen Xu: sxu1984@ustc.edu.cn, Xu-dong Jiang: Xudong@gxust.edu.cn,
DOI: 10.1038/s41401-023-01152-0
Received: 19 April 2023
Accepted: 8 August 2023
Advance online: 29 August 2023

Abstract

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.
Keywords: animal models; diabetes; HFpEF; hypertension; metabolic inflexibility; obesity

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