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Ketone body oxidation increases cardiac endothelial cell proliferation.

ABSTRACT: 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.

SUBMITTER: Weis EM

PROVIDER: S-EPMC8988203 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Ketone body oxidation increases cardiac endothelial cell proliferation.

Weis Eva-Maria EM Puchalska Patrycja P Nelson Alisa B AB Taylor Jacqueline J Moll Iris I Hasan Sana S SS Dewenter Matthias M Hagenmüller Marco M Fleming Thomas T Poschet Gernot G Hotz-Wagenblatt Agnes A Backs Johannes J Crawford Peter A PA Fischer Andreas A

EMBO molecular medicine 20220218 4

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 the ...[more]

PMID: 35179309

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Dataset Information

Ketone body oxidation increases cardiac endothelial cell proliferation.

Publications

Ketone body oxidation increases cardiac endothelial cell proliferation.

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