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Curr Opin Hematol. 2017 May;24(3):240-247. doi: 10.1097/MOH.0000000000000335.

Endothelial cell metabolism: an update anno 2017.

Author information

1
aLaboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven, Belgium bLaboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, Center for Cancer Biology (CCB), VIB, Leuven, Belgium cGZA Hospitals Sint-Augustinus, Wilrijk and Center for Oncological Research, University of Antwerp, Antwerp, Belgium.

Abstract

PURPOSE OF REVIEW:

Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications.

RECENT FINDINGS:

Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO). Glycolysis is essential as endothelial cells primarily rely on this pathway for ATP production. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a key regulator of glycolysis in endothelial cells. As endothelial cells increase glycolysis even further during angiogenesis, PFKFB3 also controls vessel sprouting and promotes endothelial cell migration. Moreover, in tumors, additional PFKFB3 upregulation leads to a more immature and dysfunctional vasculature. PFKFB3 blockade therefore results in tumor vessel normalization, with beneficial therapeutic effects on reduced metastasis and improved chemotherapy. Also, FAO stimulates endothelial cell proliferation through affecting DNA synthesis, and is critical for lymphangiogenesis, in part through epigenetic changes in histone acetylation. As FAO is controlled by carnitine palmitoyltransferase 1a, inhibition of this key enzyme decreases pathological angiogenesis.

SUMMARY:

Both PFKFB3 and carnitine palmitoyltransferase 1a are key metabolic regulators of vessel sprouting and promising new therapeutic targets in diseases associated with pathological angiogenesis.

PMID:
28212191
DOI:
10.1097/MOH.0000000000000335
[Indexed for MEDLINE]

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