Mechanical unloading is accompanied by reverse metabolic remodelling in the failing heart: Identification of a novel citraconate‐mediated pathway Article Swipe
David M. Kaye
,
Xiaosuo Wang
,
Yen Chin Koay
,
Mengbo Li
,
Bailey McIntosh
,
Yann Huey Ng
,
Michael S Rahman
,
Yiyang Cao
,
Francine Z. Marques
,
Cassandra Malecki
,
Shane Nanayakarra
,
Justin A. Mariani
,
Bing Wang
,
Sean Lal
,
Giovanni Guglielmi
,
John O’Sullivan
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/ejhf.3704
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/ejhf.3704
Aims Although functional recovery of the failing heart with left ventricular assist device (LVAD) unloading can occur, the underpinning mechanism is unclear. We aimed to characterize the effect of myocardial biochemical effect of LVAD support in vivo and in vitro . Methods and results We performed targeted metabolomics and lipidomics on transcardiac (arterial and coronary sinus) blood samples collected from healthy volunteers ( n = 13), patients with end‐stage heart failure with reduced ejection fraction (HFrEF, n = 20), and LVAD‐supported HFrEF patients ( n = 18). Complementary biochemical studies in myocardial tissue samples from healthy donor, HFrEF and LVAD patients, and cardiomyoblasts were performed. Myocardial uptake of intermediates in purine, nucleotide, and tricarboxylic acid (TCA) cycle pathways was depressed in HFrEF patients, with recovery in LVAD patients. Glucose uptake was suppressed in HFrEF but restored in LVAD. Metabolite changes suggestive of impaired fatty acid oxidation were present in HFrEF but not in LVAD. We found that the metabolite citraconate was significantly released by HFrEF hearts compared to controls and this was corroborated, in separate patients, by increased levels of citraconate in HFrEF myocardium but not in LVAD. Whilst citraconate increased succinate deydrogenase (SDH) activity in cardiomyoblasts, its isomer itaconate suppressed SDH activity. SDH activity was maintained in HFrEF myocardium but was diminished in LVAD myocardium. Conclusions We report, for the first time, the in‐vivo biochemical effects of LVAD unloading in the human heart. Our data identify citraconate as a potentially important regulator of the TCA cycle in the failing heart.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/ejhf.3704
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.3704
- OA Status
- hybrid
- Cited By
- 3
- References
- 29
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411036104
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411036104Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/ejhf.3704Digital Object Identifier
- Title
-
Mechanical unloading is accompanied by reverse metabolic remodelling in the failing heart: Identification of a novel citraconate‐mediated pathwayWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-04Full publication date if available
- Authors
-
David M. Kaye, Xiaosuo Wang, Yen Chin Koay, Mengbo Li, Bailey McIntosh, Yann Huey Ng, Michael S Rahman, Yiyang Cao, Francine Z. Marques, Cassandra Malecki, Shane Nanayakarra, Justin A. Mariani, Bing Wang, Sean Lal, Giovanni Guglielmi, John O’SullivanList of authors in order
- Landing page
-
https://doi.org/10.1002/ejhf.3704Publisher landing page
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.3704Direct link to full text PDF
- Open access
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YesWhether a free full text is available
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-
hybridOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.3704Direct OA link when available
- Concepts
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Heart failure, Medicine, Cardiology, Internal medicine, Ejection fraction, Ventricular assist device, Metabolite, In vivo, Metabolomics, Bioinformatics, Biology, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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3Total citation count in OpenAlex
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2025: 3Per-year citation counts (last 5 years)
- References (count)
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29Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.metabolomics | 47 |
| abstract_inverted_index.transcardiac | 51 |
| abstract_inverted_index.underpinning | 18 |
| abstract_inverted_index.Complementary | 87 |
| abstract_inverted_index.corroborated, | 172 |
| abstract_inverted_index.intermediates | 108 |
| abstract_inverted_index.significantly | 161 |
| abstract_inverted_index.tricarboxylic | 113 |
| abstract_inverted_index.cardiomyoblasts | 102 |
| abstract_inverted_index.LVAD‐supported | 80 |
| abstract_inverted_index.cardiomyoblasts, | 196 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 96 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 16 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8100000023841858 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.9201306 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |