Ketone body oxidation increases cardiac endothelial cell proliferation

Cardiac blood vessel growth depends on metabolic flexibility. Glucose and fatty acids are well-known energy sources for endothelial cells. However, the role of ketone bodies remains unclear. Ketone bodies are used by cardiomyocytes during fasting or ketogenic diets. This raises the question of whether endothelial cells can also use ketone bodies. Prior research has shown that these cells transport ketones, but not whether they consume them. No prior work had resolved if ketone metabolism supports endothelial proliferation. This gap motivated a closer look at ketone oxidation in cardiac endothelial cells. Understanding this could reveal new metabolic strategies for vascular growth.

This study aimed to determine if cardiac endothelial cells can oxidize ketone bodies. The researchers wanted to test if ketone metabolism supports endothelial proliferation and vessel formation. They focused on whether ketone oxidation could enhance cell migration and sprouting. The goal was to identify the enzymes and pathways involved in this process. They also sought to assess the impact of a ketogenic diet on endothelial growth. The study aimed to clarify if ketone body utilization could prevent vascular rarefaction. This would provide insight into dietary interventions for heart diseases. The work sought to bridge knowledge gaps in endothelial cell metabolism.

The researchers used cardiac endothelial cells isolated from mice. They tested ketone body oxidation using targeted metabolite profiling. They measured carbon incorporation into TCA cycle intermediates. Cell proliferation and migration were assessed using standard assays. A ketogenic diet was used to elevate ketone levels in mice. Hearts were analyzed for endothelial cell proliferation and vessel density. The study also used a heart hypertrophy model to test vascular effects. The role of succinyl-CoA:3-oxoacid-CoA transferase was evaluated in ketone oxidation.

Cardiac endothelial cells oxidized ketone bodies, which increased proliferation and migration. Ketone metabolism enhanced vessel sprouting in vitro and in vivo. Succinyl-CoA:3-oxoacid-CoA transferase was essential for this process. Carbon from ketones was incorporated into TCA cycle intermediates. This supported biomass production and energy generation. A ketogenic diet transiently increased endothelial proliferation in mouse hearts. In heart hypertrophy models, the diet prevented vascular rarefaction. These findings suggest ketone oxidation supports endothelial function.

The study shows that cardiac endothelial cells can oxidize ketone bodies. This process enhances cell proliferation and vessel sprouting. The enzyme succinyl-CoA:3-oxoacid-CoA transferase is necessary for this effect. Ketone-derived carbon fuels TCA cycle and biomass production. A ketogenic diet increases endothelial proliferation in mice. In heart hypertrophy models, the diet prevents vascular rarefaction. These findings suggest dietary ketones may support vascular health. The authors propose that ketone oxidation could be a therapeutic target.