ArticleAmerican journal of physiology. Heart and circulatory physiology2022
Cell therapy attenuates endothelial dysfunction in hypertensive rats with heart failure and preserved ejection fraction.
Article in American journal of physiology. Heart and circulatory physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Combinatorial Effect of Biomaterials and Extracellular Vesicle Therapy for Heart Failure with Reduced Ejection Fraction: A Systematic Review of Preclinical Studies.Advanced healthcare materials · 2023Pooled it
- Molecular Mechanisms Governing Vascular Function in Heart Failure.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- A new model of heart failure with preserved ejection fraction induced by metabolic syndrome in Ossabaw miniature swine.Basic research in cardiology · 2025Article
- Gene- and cell-based therapy in cardiovascular diseases.Journal of cardiovascular pharmacology · 2025Article
- Establishment of a HFpEF model using female Dahl salt-sensitive rats: a valuable tool for elucidating the pathophysiology of HFpEF in women.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction.Nature communications · 2025Article
- Taohong Siwu Decoction alleviates high salt-induced calcium overload and ferroptosis in vascular endothelial cells in hypertension by regulating ATF4.Frontiers in nutrition · 2025Article
- Molecular remodeling in comorbidities associated with heart failure: a current update.Molecular biology reports · 2024Review
- Relation between cardiac magnetic resonance-assessed interstitial fibrosis and diastolic dysfunction in heart failure due to dilated cardiomyopathy.International journal of cardiology. Heart & vasculature · 2024Article
- Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model.Basic research in cardiology · 2023Article
- Renal Denervation Helps Preserve the Ejection Fraction by Preserving Endocardial-Endothelial Function during Heart Failure.International journal of molecular sciences · 2023Article
- In Search of the Holy Grail: Stem Cell Therapy as a Novel Treatment of Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2023Review
- Systemic Delivery of Extracellular Vesicles Attenuates Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.JACC. Clinical electrophysiology · 2023Article
- A potential role of autophagy-mediated vascular senescence in the pathophysiology of HFpEF.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Heart failure with preserved ejection fraction (HFpEF) is defined by increased left ventricular (LV) stiffness, impaired vascular compliance, and fibrosis. Although systemic inflammation, driven by comorbidities, has been proposed to play a key role, the precise pathogenesis remains elusive. To test the hypothesis that inflammation drives endothelial dysfunction in HFpEF, we used cardiosphere-derived cells (CDCs), which reduce inflammation and fibrosis, improving function, structure, and survival in HFpEF rats. Dahl salt-sensitive rats fed a high-salt diet developed HFpEF, as manifested by diastolic dysfunction, systemic inflammation, and accelerated mortality. Rats were randomly allocated to receive intracoronary infusion of CDCs or vehicle. Two weeks later, inflammation, oxidative stress, and endothelial function were analyzed. Single-cell RNA sequencing of heart tissue was used to assay transcriptomic changes. CDCs improved endothelial-dependent vasodilation while reducing oxidative stress and restoring endothelial nitric oxide synthase (eNOS) expression. RNA sequencing revealed CDC-induced attenuation of pathways underlying endothelial cell leukocyte binding and innate immunity. Exposure of endothelial cells to CDC-secreted extracellular vesicles in vitro reduced VCAM-1 protein expression and attenuated monocyte adhesion and transmigration. Cell therapy with CDCs corrects diastolic dysfunction, reduces oxidative stress, and restores vascular reactivity. These findings lend credence to the hypothesis that inflammatory changes of the vascular endothelium are important, if not central, to HFpEF pathogenesis.
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