Going with the flow is a sound strategy unless, of course, something is disturbing that flow. Researchers from the Georgia Institute of Technology and Emory University have shown that when blood flow is disturbed (d-flow) there is a responsive stream of gene expression changes triggered by mechanosensitive DNA methylation.
Lead author Jessilyn Dunn shares that “It was already known previously that atherosclerosis is caused by endothelial cell dysfunction, which is characterized by a wacky gene expression profile. This gene expression change is caused by disturbed blood flow patterns that occur at branches/curves in the blood vessels, which is why plaques tend to form there rather than in the straight, unidirectional flow regions. However, its still very unclear how the global gene expression in endothelial cells changes.” Here’s what the Dunn and crew found using RRBS and arrays in their mouse model that induces d-flow by “partial carotid ligation surgery”:
- D-flow regulates genome-wide DNA methylation patterns in the endothelial cells lining arteries.
- This happens in a methyltransferase (DNMT) dependent fashion.
- 11 genes were determined to be mechanosensitive, as if responding to d-flow.
- Some of the genes were transcription factors that contained cAMP response elements.
- 5Aza treatment restored normal methylation patterns.
Based on the results, the authors believe that mechanosensitive methylation is the flow-master. Dunn concludes that this research offers a “completely novel mechanism by which the blood flow patterns regulate genome-wide DNA methylation, which in turn regulates the endothelial gene expression profile. This opens up a vast array of potential therapeutic targets for atherosclerosis.”
Go with the flow in the Journal of Clinical Investigation, June 2014