Epigenetic Change Tied to Hardening of the Arteries

New research suggests that when patterns of blood flow are disturbed, epigenetic changes occur to the genes in the cells lining blood vessels, contributing to hardening of the arteries, otherwise known as atherosclerosis. Characterized by the accumulation of inflammatory cells and fats in arteries, this disease often precedes strokes and heart attacks. Blood flow and the natural curves of the arteries are known to dictate where atherosclerotic plaques develop.

Along with his colleagues, Hanjoong Jo, a biomedical engineer and professor at The Wallace H. Coulter Department of Biomedical Engineering at GA Tech and Emory University, created a model allowing them to quickly observe the inflammatory effects caused by disturbed blood flow.

“This new study shows that disturbed blood flow induces epigenetic changes that lead to atherosclerosis,” Jo said. “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.”

Focusing on three carotid arteries on one side, the researchers restricted blood flow in mice and put them on a high-fat, traditional ‘Western’ diet. The results, which were published in the Journal of Clinical Investigation, demonstrate that disturbed blood flow “controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.”

His team also showed, using their mouse model, that a drug interrupting DNA methylation can block the blood flow patterns seen in atherosclerosis. They identified several genes that are turned off when blood flow is disturbed, representing new possible therapeutic targets for this increasingly prevalent disease.

They found that the same drug used for treating acute myeloid leukemia, 5-aza-2′-deoxycytidine, can prevent the formation of atherosclerotic plaques in the mouse model.
“While we do not envision using 5-aza for atherosclerosis treatment clinically, our results do reveal potential therapeutic targets,” Jo said.

A broader message of the study is that by improving blood flow patterns, such as through exercise, you can have a lasting, positive effect on gene expression in the blood vessels.

Source: Learn all about it and read more about their findings here: Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. 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.

References: Emory Health Sciences. Disturbance in Blood Flow Leads to Epigenetic Changes and Atherosclerosis. 27 May 2014.