Disturbance in blood flow leads to epigenetic changes, atherosclerosis

"This new study shows that disturbed blood flow induces epigenetic changes that lead to atherosclerosis," Jo says. "It had been known for a long time that plaques preferentially develop in curved and branched arteries, but our lab has been able to prove that disturbed blood flow can actually trigger atherosclerosis, in the presence of risk factors such as high blood cholesterol."
Despite the demonstrated importance of blood flow patterns in atherosclerosis, it can be blocked in mouse models with a drug that interrupts the process of DNA methylation, an epigenetic change that often turns genes off. Jo's team has identified several genes that become turned off under disturbed flow conditions, in a way that requires DNA methylation. Some of these genes may represent new therapeutic targets in atherosclerosis.
Dunn and her colleagues found that treatment with 5-aza-2'-deoxycytidine, a drug that is now used to treat acute myeloid leukemia, can prevent atherosclerotic plaques from forming in the mouse model.
"While we do not envision using 5-aza for atherosclerosis treatment clinically, our results do reveal potential therapeutic targets," Jo says.

Story Source:
The above story is based on materials provided by Emory Health SciencesNote: Materials may be edited for content and length.

Journal Reference:
  1. Jessilyn Dunn, Haiwei Qiu, Soyeon Kim, Daudi Jjingo, Ryan Hoffman, Chan Woo Kim, Inhwan Jang, Dong Ju Son, Daniel Kim, Chenyi Pan, Yuhong Fan, I. King Jordan, Hanjoong Jo. Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosisJournal of Clinical Investigation, 2014; DOI: 10.1172/JCI74792


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