Targeting endothelial cell metabolism: new therapeutic prospects?

Abstract

Endothelial cells (ECs) line blood vessels and function as a vital conduit for oxygen and nutrients, but can also form vascular niches for various types of stem cells. While mostly quiescent throughout adult life, ECs can rapidly switch to a highly active state, and start to sprout in order to form new blood vessels. ECs can also become dysfunctional, as occurs in diabetes and atherosclerosis. Recent studies have demonstrated a key role for EC metabolism in the regulation of angiogenesis, and showed that EC metabolism is even capable of overriding genetic signals. In this review, we will review the basic principles of EC metabolism and focus on the metabolic alterations that accompany EC dysfunction in diabetes and vessel overgrowth in cancer. We will also highlight how EC metabolism influences EC behavior by modulating post-translational modification and epigenetic changes, and illustrate how dietary supplementation of metabolites can change EC responses. Finally, we will discuss the potential of targeting EC metabolism as a novel therapeutic strategy.

Keywords

angiogenesis / metabolism / endothelial cell dysfunction / anti-angiogenic therapy

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Acknowledgments

We apologize for not being able to cite the work of all other studies related to this topic because of space restrictions. The authors gratefully acknowledge Guy Eelen, Jermaine Goveia and Brian Wong for valuable comments. A.B. is PhD student supported by an Erasmus Mundus Western Balkans (ERAWEB) scholarship. The work of P.C. is supported by a Federal Government Belgium grant (IUAP P7/03), long-term structural Methusalem funding by the Flemish Government, the Research Foundation Flanders (FWO), the Foundation Leducq Transatlantic Network (ARTEMIS), Foundation against cancer, an European Research Council (ERC) Advanced Research Grant (EU-ERC269073) and the AXA Research Fund.

Compliance with ethics <?Pub Caret?>guidelines

Peter Carmeliet is named as an inventor on patent application regarding subject matter related to the findings reviewed in this publication. Annalisa Zecchin and Aleksandra Brajic declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review boards or ethics committees.

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