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Abstract
Recently, endothelial cell metabolism has emerged as an essential driver and regulator
of both blood and lymph vessel development. Evidence rapidly builds that metabolism
is not only necessary for endothelial cell function, but moreover controls several
aspects of the (lymph)-angiogenic process. So far, the best-characterized metabolic
pathways to have an impact on angiogenesis are glycolysis, fatty acid oxidation and
glutamine metabolism. Glycolysis regulates tip cell behavior by providing ATP, fatty
acid oxidation controls stalk cell proliferation by producing nucleotide biomass,
and glutamine metabolism is critical for tip and stalk cell dynamics by supporting
Krebs cycle anaplerosis, protein production and redox homeostasis, and links to asparagine
metabolism. During lymphangiogenesis, glycolysis and fatty acid oxidation are key
metabolic pathways. Glycolysis provides energy for growing lymph vessels, while fatty
acid oxidation is a critical metabolic regulator of lymphangiogenesis, in part by
promoting nucleotide synthesis as well as by mediating epigenetic changes of histone
acetylation, which promotes transcription of key lymphatic genes, and hence venous-to-lymphatic
endothelial cell differentiation. On the whole, increasing knowledge on the metabolic
landscape of endothelial cells offers a fresh impetus to future treatment possibilities
of vascular related diseases.