Trends in Cell Biology
ReviewEndothelial Cell Metabolism in Health and Disease
Section snippets
Angiogenesis: From Quiescent Cells to a New Vessel Sprout
ECs form the inner lining of blood and lymphatic vessels and are essential for normal functioning of the vascular system. The vascular network expands in response to changing metabolic demands during physiological organ growth to supply all tissues with sufficient oxygen and nutrients. Throughout adulthood, ECs stay mostly quiescent; however, they retain the capacity to rapidly initiate new vessel formation in response to injury or in pathological conditions. This tightly regulated process,
Glycolysis Is the Main Energy Source in the Endothelium
ECs are glycolysis addicts, since 85% of their ATP is produced glycolytically by converting glucose to lactate [3]. Compared with many other healthy cell types, ECs have higher rates of glycolysis and their glucose consumption is in the same range as that of many cancer cells [3]. Even though oxidative metabolism yields 34 extra molecules of ATP from one molecule of glucose, only a small fraction of pyruvate generated from glycolysis is metabolized oxidatively [3]. At first sight, it might seem
Metabolism of Tumor Endothelium
Blood vessels promote multiple inflammatory and malignant diseases. Emerging evidence suggests that the metabolism of ECs in these disorders is perturbed. For reasons of brevity, we focus here on cancer, and refer readers to Box 1 for other vascular disorders (including diabetes). Cancer cells stimulate angiogenesis to supply oxygen and nutrients. However, unlike in healthy tissue, blood vessels in tumors are disorganized, excessive in number, and dysfunctional [31]. Indeed, due to its abnormal
Metabolic Crosstalk between Endothelium and Other Cell Types
While metabolism of individual cell types in the TME are a focus of intense research, how these various cell types communicate with each other via nutrient and metabolite exchange remains understudied. Cells in the TME experience selective pressure, in part due to the lack of nutrients and increased accumulation of metabolic waste products, caused to some extent by inefficient blood perfusion. These conditions alter the secretome of the cell, excreted directly or via exosomes [51].
ECs engage in
Concluding Remarks
EC metabolism is a key regulator of angiogenesis, and represents an attractive therapeutic target. Although overlooked for decades, substantial perturbations of the metabolism of tumor ECs and of the endothelium in other vascular diseases were recently documented. These differences between normal and diseased ECs might offer novel therapeutic opportunities for improved antiangiogenesis medication. Another level of opportunity relates to targeting metabolic crosstalk between ECs, cancer cells,
Author Contributions
All authors prepared and revised the manuscript, and approved the final version; K.R. and K.V. prepared the figures.
Disclaimer Statement
P.C. is named as an inventor on patent applications related to the results described in this manuscript.
Acknowledgments
The authors apologize to any author whose work could not be included due to space limitations. K.R. and K.V. are supported by the Research Foundation Flanders (FWO). The work of P.C. is supported by a Belgian Science Policy grant (IUAP7/03), long-term structural Methusalem funding by the Flemish Government, grants from the FWO (G.0834.13N and G.0532.10N), Foundation against Cancer (grant no. 2012-175), a European Research Council (ERC) Advanced Research Grant (EU ERC269073), and an AXA Research
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