Acetyl-CoA role in lymphangiogenesis

Author: Endonita Hajzeraj

The Beta-oxidation of endothelial cells produces Acetyl-CoA, needed for epigenetic modifications for lymphangiogenesis.
Endonita Hajzeraj
Bcm441
Acetyl-CoA is an important coenzyme that participates in many biochemical reactions in metabolism. One of it’s main functions is in the Krebs cycle where the acetyl group is oxidized to carbon dioxide and water and energy is released. With its multifaceted skills, acetyl-CoA contributes to many reactions that occur in our bodies. In a research publishes in Nature, Wong et al. determined the role of fatty acid beta-oxidation in endothelial cells. They determined that fatty acid beta-oxidation in endothelial cells generates acetyl-CoA which it then uses for histone acetylation. Histone acetylation is the process by which the lysine residues from the histone core of the nucleosome. This is typically done with the acetyl group from acetyl-CoA being transferred to lysine. This will stimulate transcription to occur.
Wong et al. determined the steps of the fatty acid beta-oxidation process that is linked to CoA. CPT1, is used to convert the fatty acyl-CoA into fatty acyl-carnitine, where it will enter the mitochondrial matrix and eventually regenerate fatty acyl-CoA and convert that into acetyl-CoA. Wong and colleagues wanted to examine the Fatty acid oxidation in lymphatic endothelial cells. The lymphatic system is required for immune function, lipid absorption, and clearing out interstitial fluid. To understand the oxidation in lymphatic endothelial cells, then lymphangiogenesis, the formation of lymphatic vessels, is important in physiology.
The three different forms of the carnitine enzyme, CPT1A, CPT1B, and CPT1C differ amongst their distribution in tissues. Wong and colleagues conducted tests to see which of the three isoforms of carnitine was observed along with increased expression of fatty acid oxidation. They determined that CPT1A might be required for lymphangiogenesis. They determined that a disruption in CPT1A blocks lymphangiogenesis, which suggests that lipid transport across the membrane is needed for this process to occur. The authors see that the loss of CPT1A activity alters the expression of lymphatic endothelial cells markers and that histone acetylation is decreased in cells that did not contain CPT1A. The authors also determined that Prox1, which induces CPTA1 expression, binds p300 histone acetyltransferase to enhance acetylation of LEC genes, which enables differentiation.
The authors argue that endothelial cell growth and differentiation is dependent on fatty acid oxidation and it is possible that it is most important to endothelial cells. There are other cells that are dependent on acetyl-CoA, and while FAO has shown to be important for histone acetylation in lymphangiogenesis, the other directions of acetyl-CoA will be questioned in future work.

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