Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2020 May 12;10:7849. doi: 10.1038/s41598-020-63900-0

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Schematic summary of VEGF-A- and GW0742-induced metabolic activation in dynamic HUVEC. (a) Treatment with VEGF-A is characterised by a significantly high rate of glycolysis which provides ATP for migration and activation of biosynthetic side-pathways for proliferation. At the same time, mitochondrial fatty acid oxidation (FAO) is maintained, which may further support proliferation through acting as an additional source of carbon. Key metabolites can also influence angiogenesis-related signalling pathways while Akt, through inhibitory phosphorylation, can inactivate the anti-proliferative transcription factor, FOXO1. (b) GW0742-induced tubulogenesis is SIRT1-dependent and characterised by a significant increase in mitochondrial FAO in addition to a moderate increase in glycolysis. Elevated acetyl-CoA levels may act as a substrate for post-translational protein acetylation (indicated in the figure by ) which could facilitate PPARβ/δ transcriptional activity and influence angiogenesis-related signalling pathways. FAO may also contribute to the regulation of EC permeability and thus may have a role in neovessel maturation/stabilisation. Thickness of arrows indicate increased flux while broken arrows indicate pathways that remain to be established.

Inline graphic — Schematic summary of VEGF-A- and GW0742-induced metabolic activation in dynamic HUVEC. (a) Treatment with VEGF-A is characterised by a significantly high rate of glycolysis which provides ATP for migration and activation of biosynthetic side-pathways for proliferation. At the same time, mitochondrial fatty acid oxidation (FAO) is maintained, which may further support proliferation through acting as an additional source of carbon. Key metabolites can also influence angiogenesis-related signalling pathways while Akt, through inhibitory phosphorylation, can inactivate the anti-proliferative transcription factor, FOXO1. (b) GW0742-induced tubulogenesis is SIRT1-dependent and characterised by a significant increase in mitochondrial FAO in addition to a moderate increase in glycolysis. Elevated acetyl-CoA levels may act as a substrate for post-translational protein acetylation (indicated in the figure by ) which could facilitate PPARβ/δ transcriptional activity and influence angiogenesis-related signalling pathways. FAO may also contribute to the regulation of EC permeability and thus may have a role in neovessel maturation/stabilisation. Thickness of arrows indicate increased flux while broken arrows indicate pathways that remain to be established.