Endothelial cell metabolism: an update anno 2017. Issue 3 (May 2017)

• Record Type: Journal Article
• Authors: Teuwen, Laure-Anne; Draoui, Nihed; Dubois, Charlotte; Carmeliet, Peter
• Is Part Of: Current opinion in hematology. Volume 24:Issue 3(2017:May)
• Publication Date: 2017-05
• Subjects: angiogenesis -- carnitine palmitoyltransferase 1a -- endothelial cell metabolism -- forkhead box O 1 -- 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1097/MOH.0000000000000335
• Languages: English
• ISSNs: 1065-6251

Abstract

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.