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.

中文翻译：

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酮体氧化增加心脏内皮细胞增殖

血管形成依赖于内皮细胞的代谢适应。葡萄糖和脂肪酸是 ATP 和生物质生产的重要底物；然而，其他底物的代谢仍然知之甚少。在饥饿或消耗碳水化合物限制性饮食期间，酮体是心肌细胞的重要营养素。这就提出了一个问题，即心脏内皮细胞是否不仅会运输酮体，还会消耗其中的一些来满足其代谢需求。在这里，我们报告心脏内皮细胞能够氧化酮体，这会增强细胞增殖、迁移和血管发芽。从机制上讲，这需要琥珀酰辅酶A：3-含氧酸辅酶A转移酶，这是酮体氧化的关键酶。有针对性的代谢物分析表明，酮体中的碳被纳入三羧酸循环中间体以及其他促进生物质生产的代谢物。通过高脂肪、低碳水化合物的生酮饮食提高酮体水平会暂时增加小鼠心脏的内皮细胞增殖。值得注意的是，在心脏肥大的小鼠模型中，生酮饮食可防止血管稀疏。这表明饮食干预在心脏病中具有潜在的有益作用。生酮饮食可防止血管稀疏。这表明饮食干预在心脏病中具有潜在的有益作用。生酮饮食可防止血管稀疏。这表明饮食干预在心脏病中具有潜在的有益作用。