Featured Research

from universities, journals, and other organizations

Disturbance in blood flow leads to epigenetic changes, atherosclerosis

Date:
May 27, 2014
Source:
Emory Health Sciences
Summary:
Disturbed patterns of blood flow induce lasting epigenetic changes to genes in the cells that line blood vessels, and those changes contribute to atherosclerosis, researchers have found. The findings suggest why the protective effects of good blood flow patterns, which aerobic exercise promotes, can persist over time.

This image shows the effects of 5aza on atherosclerosis model.
Credit: Dunn et al JCI (2014)

Disturbed patterns of blood flow induce lasting epigenetic changes to genes in the cells that line blood vessels, and those changes contribute to atherosclerosis, researchers have found. The findings suggest why the protective effects of good blood flow patterns, which aerobic exercise promotes, can persist over time. An epigenetic change to DNA is a chemical modification that alters whether nearby genes are likely to be turned on or off, but not the letter-by-letter sequence itself.

The results are scheduled for publication in the Journal of Clinical Investigation.

Atherosclerosis is the buildup of fats and inflammatory cells in arteries, a process that can lead to heart attacks and strokes. The curvature of arteries and resulting disturbed flow influence where atherosclerotic plaques develop. Biomedical engineer Hanjoong Jo and his colleagues have developed a model that allows them to see the inflammatory effects of disturbed blood flow quickly. Jo is professor of biomedical engineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

"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.

The co-first authors of the JCI paper are biomedical engineering graduate students Jessilyn Dunn and Haiwei Qiu, and postdoc Soyeon Kim, PhD.

In the Jo lab's mouse model, researchers restrict blood flow in three carotid arteries on one side, in the presence of a high-fat diet. In a 2010 paper in Blood, they had found that one of the genes induced by disturbed blood flow is DNMT1, encoding a DNA methyltransferase enzyme.

DNMT1 carries out DNA methylation, an epigenetic modification of DNA. Changes in DNA methylation are important for cells differentiating into different tissues such as blood, muscle or bone, and for the development of cancer.

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.

A broader implication is that improving blood flow patterns, through aerobic exercise for example, can induce a lasting imprint on gene expression in the blood vessels, he says.


Story Source:

The above story is based on materials provided by Emory Health Sciences. Note: 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 atherosclerosis. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI74792

Cite This Page:

Emory Health Sciences. "Disturbance in blood flow leads to epigenetic changes, atherosclerosis." ScienceDaily. ScienceDaily, 27 May 2014. <www.sciencedaily.com/releases/2014/05/140527185355.htm>.
Emory Health Sciences. (2014, May 27). Disturbance in blood flow leads to epigenetic changes, atherosclerosis. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2014/05/140527185355.htm
Emory Health Sciences. "Disturbance in blood flow leads to epigenetic changes, atherosclerosis." ScienceDaily. www.sciencedaily.com/releases/2014/05/140527185355.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins