Angiogenesis is the process by which new blood vessels branch off and grow from existing vessels. In order for this process to take place successfully, endothelial cells must migrate and proliferate in a specific way. An article written by Schoors, et al,1 reports that unlike most other cells, these endothelial cells obtain the carbon required for proliferation from the oxidative breakdown of fatty acids. The mitochondrial process of b-oxidation, breaks fatty acids down into two-carbon units called Acetyl CoA, a molecule with many different functions throughout the body. Acetyl CoA is used in a primary manner of regulating DNA transcription. The Acetyl group from Acetyl-CoA is transferred to a histone protein, reducing its positive charge, and loosening its interaction with the DNA molecule, making it more accessible for transcription. Acetyl CoA also serves as the primary source of carbon for one of the most important metabolic procedures for producing cellular energy, the citric acid cycle. Schoors, et al, 1 reports a previously unknown role of Acetyl CoA, in which it serves as a source of carbon for the replication of DNA that occurs during proliferation of Endothelial cells. In order to investigate the roles of Acetyl CoA and b-oxidation in the proliferation of Endothelial cells, the authors silenced a rate-limiting enzyme called carnitine palmitoyltransferase 1A (CPT1A) which is required for fatty acids to enter the mitochondria for catabolism. Cells containing the mutant enzyme were unable to divide, but there was little change in the amount of energy produced by the cells. Upon examination of the cell contents, Schoor, et al, 1 found that the disruption of the enzyme had no effect on the cell’s production of proteins or RNA, however it revealed a deficiency in the dNTP precursors for DNA synthesis. The researchers were able to reverse this effect by supplying the cell with either dNTPs or acetate. This data confirmed that Acetyl CoA produced by oxidation of Fatty Acids is required for the synthesis of dNTPs by endothelial cells. The results obtained by Schoors, et al, 1 are significant in that they provide a method by which to inhibit angiogenesis. Various diseases such as pathological ocular angiogenesis are caused by uncontrolled growth of blood vessels, and could therefore potentially be treated by disrupting fatty acid oxidation in relevent endothelial cells.
- Schoors, S. et al. Nature 520,192–197 (2015).
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