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Ketone body oxidation increases cardiac endothelial cell proliferation

Blood vessel formation is dependent on metabolic adaption in endothelial cells. Glucose and fatty acids are essential substrates for ATP and biomass production; however, the metabolism of other substrates remains poorly understood. Ketone bodies are important nutrients for cardiomyocytes during star...

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Main Authors: Weis, Eva-Maria (Author) , Puchalska, Patrycja (Author) , Nelson, Alisa B (Author) , Taylor, Jacqueline (Author) , Moll, Iris (Author) , Safatul Hasan, Sana (Author) , Dewenter, Matthias (Author) , Hagenmüller, Marco (Author) , Fleming, Thomas (Author) , Poschet, Gernot (Author) , Hotz-Wagenblatt, Agnes (Author) , Backs, Johannes (Author) , Crawford, Peter A (Author) , Fischer, Andreas (Author)
Format: Article (Journal)
Language:English
Published: Apr 2022
In: EMBO molecular medicine
Year: 2022, Volume: 14, Issue: 4, Pages: 1-18
ISSN:1757-4684
DOI:10.15252/emmm.202114753
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/emmm.202114753
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/emmm.202114753
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Author Notes:Eva‐Maria Weis, Patrycja Puchalska, Alisa B Nelson, Jacqueline Taylor, Iris Moll, Sana S Hasan, Matthias Dewenter, Marco Hagenmüller, Thomas Fleming, Gernot Poschet, Agnes Hotz‐Wagenblatt, Johannes Backs, Peter A Crawford and Andreas Fischer
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Summary:Blood vessel formation is dependent on metabolic adaption in endothelial cells. Glucose and fatty acids are essential substrates for ATP and biomass production; however, the metabolism of other substrates remains poorly understood. Ketone bodies are important nutrients for cardiomyocytes during starvation or consumption of carbohydrate‐restrictive diets. This raises the question whether cardiac endothelial cells would not only transport ketone bodies but also consume some of these to achieve their metabolic needs. Here, we report that cardiac endothelial cells are able to oxidize ketone bodies and that this enhances cell proliferation, migration, and vessel sprouting. Mechanistically, this requires succinyl‐CoA:3‐oxoacid‐CoA transferase, a key enzyme of ketone body oxidation. Targeted metabolite profiling revealed that carbon from ketone bodies got incorporated into tricarboxylic acid cycle intermediates as well as other metabolites fueling biomass production. Elevation of ketone body levels by a high‐fat, low‐carbohydrate ketogenic diet transiently increased endothelial cell proliferation in mouse hearts. Notably, in a mouse model of heart hypertrophy, ketogenic diet prevented blood vessel rarefication. This suggests a potential beneficial role of dietary intervention in heart diseases.
Item Description:Online veröffentlicht: 18 February 2022
Gesehen am 26.03.2024
Physical Description:Online Resource
ISSN:1757-4684
DOI:10.15252/emmm.202114753

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