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Nature reviews. CardiologyReview

09 May 2025

Endothelial cell metabolism in cardiovascular physiology and disease.

Abstract

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.

COI Statement

Competing interests: The authors declare no competing interests.

References:

  • Eelen, G. et al. Endothelial cell metabolism. Physiol. Rev. 98, 3–58 (2018).
  • Potente, M. & Carmeliet, P. The link between angiogenesis and endothelial metabolism. Annu. Rev. Physiol. 79, 43–66 (2017).
  • Trimm, E. & Red-Horse, K. Vascular endothelial cell development and diversity. Nat. Rev. Cardiol. 20, 197–210 (2023).
  • Siragusa, M. et al. Nitric oxide maintains endothelial redox homeostasis through PKM2 inhibition. EMBO J. 38, e100938 (2019).
  • Schoors, S. et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520, 192–197 (2015).

Article info

Journal issue:

  • Volume: not provided
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Doi:

10.1038/s41569-025-01162-x

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