Featured Research

from universities, journals, and other organizations

Root cause of blood vessel damage in diabetes discovered

Date:
February 11, 2011
Source:
Washington University School of Medicine
Summary:
Diabetes researchers have identified a key mechanism that appears to contribute to the blood vessel damage that occurs in people with diabetes. Blood vessel problems are a common diabetes complication. Many of the nearly 26 million Americans with the disease face the prospect of amputations, heart attack, stroke and vision loss because of damaged vessels.

Blood flow was interrupted in a vessel in normal mice (above) and in FASTie mice (below). After a few weeks, the normal mice formed new blood vessels to restore blood flow, but FASTie mice without fatty acid synthase did not.
Credit: Semenkovich lab, Washington University School of Medicine

A key mechanism that appears to contribute to blood vessel damage in people with diabetes has been identified by researchers at Washington University School of Medicine in St. Louis.

Blood vessel problems are a common diabetes complication. Many of the nearly 26 million Americans with the disease face the prospect of amputations, heart attack, stroke and vision loss because of damaged vessels.

Reporting in the Journal of Biological Chemistry, the Washington University researchers say studies in mice show that the damage appears to involve two enzymes, fatty acid synthase (FAS) and nitric oxide synthase (NOS), that interact in the cells that line blood vessel walls.

"We already knew that in diabetes there's a defect in the endothelial cells that line the blood vessels," says first author Xiaochao Wei, PhD. "People with diabetes also have depressed levels of fatty acid synthase. But this is the first time we've been able to link those observations together."

Wei is a postdoctoral research scholar in the lab of Clay F. Semenkovich, MD, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and chief of the Division of Endocrinology, Metabolism and Lipid Research.

Wei studied mice that had been genetically engineered to make FAS in all of their tissues except the endothelial cells that line blood vessels. These so-called FASTie mice experienced problems in the vessels that were similar to those seen in animals with diabetes.

"It turns out that there are strong parallels between the complete absence of FAS and the deficiencies in FAS induced by lack of insulin and by insulin resistance," Semenkovich says.

Comparing FASTie mice to normal animals, as well as to mice with diabetes, Wei and Semenkovich determined that mice without FAS, and with low levels of FAS, could not make the substance that anchors nitric oxide synthase to the endothelial cells in blood vessels.

"We've known for many years that to have an effect, NOS has to be anchored to the wall of the vessel," Semenkovich says. "Xiaochao discovered that fatty acid synthase preferentially makes a lipid that attaches to NOS, allowing it to hook to the cell membrane and to produce normal, healthy blood vessels."

In the FASTie mice, blood vessels were leaky, and in cases when the vessel was injured, the mice were unable to generate new blood vessel growth.

The actual mechanism involved in binding NOS to the endothelial cells is called palmitoylation. Without FAS, the genetically engineered mice lose NOS palmitoylation and are unable to modify NOS so that it will interact with the endothelial cell membrane. That results in blood vessel problems.

"In animals that don't have fatty acid synthase and normal nitric oxide synthase in endothelial cells, we saw a lot of leaky blood vessels," Semenkovich explains. "The mice also were more susceptible to the consequences of infection, and they couldn't repair damage that occurred -- problems that also tend to be common in people with diabetes."

In one set of experiments, the researchers interrupted blood flow in the leg of a normal mouse and in a FASTie mouse.

"The control animals regained blood vessel formation promptly," Semenkovich says, "but that did not happen in the animals that were modified to be missing fatty acid synthase."

It's a long way, however, from a mouse to a person, so the researchers next looked at human endothelial cells, and they found that a similar mechanism was at work.

"Our findings strongly suggest that if we can use a drug or another enzyme to promote fatty acid synthase activity, specifically in blood vessels, it might be helpful to patients with diabetes," Wei says. "We also have been able to demonstrate that palmitoylation of nitric oxide synthase is impaired in diabetes, and if we can find a way to promote the palmitoylation of NOS, even independent of fatty acid synthase, it may be possible to treat some of the vascular complications of diabetes."

And it shouldn't matter whether a person has type 1 diabetes and can't manufacture insulin or the more common type 2 diabetes, in which a person becomes resistant to insulin.

"That's one of the key findings," Semenkovich says. "It won't matter whether it's an absence of insulin or resistance to insulin: both are associated with defects in FAS."


Story Source:

The above story is based on materials provided by Washington University School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. X. Wei, J. G. Schneider, S. M. Shenouda, A. Lee, D. A. Towler, M. V. Chakravarthy, J. A. Vita, C. F. Semenkovich. De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation. Journal of Biological Chemistry, 2010; 286 (4): 2933 DOI: 10.1074/jbc.M110.193037

Cite This Page:

Washington University School of Medicine. "Root cause of blood vessel damage in diabetes discovered." ScienceDaily. ScienceDaily, 11 February 2011. <www.sciencedaily.com/releases/2011/01/110129081530.htm>.
Washington University School of Medicine. (2011, February 11). Root cause of blood vessel damage in diabetes discovered. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2011/01/110129081530.htm
Washington University School of Medicine. "Root cause of blood vessel damage in diabetes discovered." ScienceDaily. www.sciencedaily.com/releases/2011/01/110129081530.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Quintuplets Head Home

Texas Quintuplets Head Home

Reuters - US Online Video (Aug. 1, 2014) After four months in the hospital, the first quintuplets to be born at Baylor University Medical Center head home. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Patient Coming to U.S. for Treatment

Ebola Patient Coming to U.S. for Treatment

Reuters - US Online Video (Aug. 1, 2014) A U.S. aid worker infected with Ebola while working in West Africa will be treated in a high security ward at Emory University in Atlanta. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
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:
from the past week

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