Pasut Alessandra, Lama Eleonora, Van Craenenbroeck Amaryllis H, Kroon Jeffrey, Carmeliet Peter
Laboratory of Angiogenesis & Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, VIB, Leuven, Belgium.
Division of Nephrology, University Hospitals Leuven, Leuven, Belgium.
Nat Rev Cardiol. 2025 May 9. doi: 10.1038/s41569-025-01162-x.
Endothelial cells are multifunctional cells that form the inner layer of blood vessels and have a crucial role in vasoreactivity, angiogenesis, immunomodulation, nutrient uptake and coagulation. Endothelial cells have unique metabolism and are metabolically heterogeneous. The microenvironment and metabolism of endothelial cells contribute to endothelial cell heterogeneity and metabolic specialization. Endothelial cell dysfunction is an early event in the development of several cardiovascular diseases and has been shown, at least to some extent, to be driven by metabolic changes preceding the manifestation of clinical symptoms. Diabetes mellitus, hypertension, obesity and chronic kidney disease are all risk factors for cardiovascular disease. Changes in endothelial cell metabolism induced by these cardiometabolic stressors accelerate the accumulation of dysfunctional endothelial cells in tissues and the development of cardiovascular disease. In this Review, we discuss the diversity of metabolic programmes that control endothelial cell function in the cardiovascular system and how these metabolic programmes are perturbed in different cardiovascular diseases in a disease-specific manner. Finally, we discuss the potential and challenges of targeting endothelial cell metabolism for the treatment of cardiovascular diseases.
内皮细胞是构成血管内层的多功能细胞，在血管反应性、血管生成、免疫调节、营养摄取和凝血过程中发挥着关键作用。内皮细胞具有独特的代谢且代谢具有异质性。内皮细胞的微环境和代谢促成了内皮细胞的异质性和代谢特化。内皮细胞功能障碍是多种心血管疾病发展过程中的早期事件，并且已表明至少在一定程度上是由临床症状出现之前的代谢变化所驱动。糖尿病、高血压、肥胖症和慢性肾脏病都是心血管疾病的危险因素。这些心脏代谢应激源引起的内皮细胞代谢变化加速了组织中功能失调的内皮细胞的积累以及心血管疾病的发展。在本综述中，我们讨论了控制心血管系统中内皮细胞功能的代谢程序的多样性，以及这些代谢程序在不同心血管疾病中如何以疾病特异性方式受到干扰。最后，我们讨论了针对内皮细胞代谢治疗心血管疾病的潜力和挑战。
