Molecular Signature of HFpEF

Gibb, Andrew; Murray, Emma K; Eaton, Deborah; Huynh, Anh; Tomar, Dhanendra; Garbincius, Joanne F; Kolmetzky, Devin W.; Berretta, Remus; Wallner, Markus; Houser, Steven R.; Elrod, John W.

doi:10.1016/j.jacbts.2021.07.004

Cited by 17 publications

(3 citation statements)

References 78 publications

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“…A systems biology approach involving metabolomics and transcriptomics was used to assess HFpEF progression in the domestic cat subjected to aortic banding. 65 In this nonobese HFpEF model, cardiac hypertrophy and fibrosis occur at 1 month before diastolic dysfunction, and a few genes related to metabolism, including some associated with the mitochondrial ETC, were found to be altered at that time. Cardiac mitochondrial function was impaired, which along with the metabolic changes indicated impaired oxidative phosphorylation.…”

Section: Introductionmentioning

confidence: 78%

“…These studies highlight the growing awareness that mitochondrial dysfunction is a common feature of HFpEF, particularly where diabetes and obesity are involved. 43,65,72 Whether mitochondrial dysfunction is causative or a consequence is yet to be established. Although no studies today have reported on MAMs in HFpEF, a better understanding of the processes by which mitochondria and ER/SR communicate is needed.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

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What Role do Mitochondria Have in Diastolic Dysfunction? Implications for Diabetic Cardiomyopathy and Heart Failure With Preserved Ejection Function

McCandless

Altara

Booz

et al. 2022

Journal of Cardiovascular Pharmacology

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:Diastolic dysfunction is common to both diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). Although commonly attributed to increased fibrosis, alterations in mitochondrial function and associated Ca2+ handling may contribute to impaired cardiac function. With mitochondrial dysfunction, increased reactive oxygen species (ROS), inflammation, and decreased adenosine triphosphate/adenosine diphosphate ratio may lead to increased extracellular matrix and diminished contractile relaxation. In this article, we discuss recent research implicating deficient mitochondria-associated endoplasmic reticulum membranes (MAMs) as it relates to impaired metabolic function and what role that may have in diastolic dysfunction in diabetic cardiomyopathy. The contribution of mitochondrial dysfunction to diastolic dysfunction in HFpEF is less established, but equally credible based on preclinical studies. However, there are notable differences between diabetic cardiomyopathy and HFpEF. Recent evidence implicates impaired endoplasmic reticulum signaling, in particular the unfolded protein response (UPR), in the pathogenesis of HFpEF. With HFpEF, enhanced pressure on the mitochondrial “gas pedal” because of increased cytosolic Ca2+ may perturb mitochondrial homeostasis. For diabetic cardiomyopathy and HFpEF, a better understanding of how altered cellular ion and redox status affect mitochondrial function is needed. Finally, we discuss the implications that mitochondrial dysfunction may have in devising novel therapeutic strategies for diabetic cardiomyopathy and HFpEF.

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Section: Introductionmentioning

confidence: 78%

Section: Therapeutic Implicationsmentioning

confidence: 99%

What Role do Mitochondria Have in Diastolic Dysfunction? Implications for Diabetic Cardiomyopathy and Heart Failure With Preserved Ejection Function

McCandless

Altara

Booz

et al. 2022

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

show abstract

“…Early large animal models of HFpEF were based on single-hit perturbations, such as pressure overload in sheep ( Charles et al, 1996 ) or canine model of mild coronary microembolizations ( He et al, 2004 ), and exhibit only a portion of HFpEF features. Recently, slow-progressive pressure overload by aortic-constriction was used to establish a feline HFpEF model ( Wallner et al, 2017 ; Wallner et al, 2020 ; Gibb et al, 2021 ). Comprehensive phenotyping of this model showed many features of HFpEF, such as concentric LV hypertrophy and significant diastolic dysfunction ( Wallner et al, 2017 ; Wallner et al, 2020 ).…”

Section: Large Animal Models Of Hfpefmentioning

confidence: 99%

Age and Sex Differences in Heart Failure With Preserved Ejection Fraction

2022

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Heart failure with preserved ejection fraction (HFpEF) is a multi-organ disorder that represents about 50% of total heart failure (HF) cases and is the most common form of HF in the elderly. Because of its increasing prevalence caused by the aging population, high mortality and morbidity, and very limited therapeutic options, HFpEF is considered as one of the greatest unmet medical needs in cardiovascular medicine. Despite its complex pathophysiology, numerous preclinical models have been established in rodents and in large animals to study HFpEF pathophysiology. Although age and sex differences are well described in HFpEF population, there are knowledge gaps in sex- and age-specific differences in established preclinical models. In this review, we summarize various strategies that have been used to develop HFpEF models and discuss the knowledge gaps in sex and age differences in HFpEF.

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