Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study pinpoints new role of molecule in the health of body's back-up blood circulation

26.05.2010
When the arteries delivering oxygen to our vital organs are obstructed by atherosclerosis or clots, the result is almost always a stroke, heart attack or damage to a peripheral tissue such as the legs (peripheral artery disease).

t the severity of tissue injury or destruction from a choked-off blood supply varies from person to person, and may depend in large part on whose circulatory system has the best back-up plan to provide alternate routes of circulation.

This "back-up system" – called the collateral circulation – involves a small number of tiny specialized blood vessels, called collaterals, that can enlarge their diameters enough to carry significant flow and thus bypass a blockage.

Researchers at the University of North Carolina at Chapel Hill School of Medicine have now discovered that the abundance of these vessels in a healthy individual and their growth or remodeling into "natural bypass vessels" depends on how much of a key signaling molecule -- called nitric oxide -- is present.

The study, conducted in animal models, suggests that nitric oxide not only is critical in maintaining the number of collateral vessels while individuals are healthy. It also is key in the amount of collateral vessel remodeling that occurs when obstructive disease strikes.

The research findings recently appeared online in the journal Circulation Research and will be published in the print edition on June 25th. They could one day enable researchers to predict people's risk for catastrophic stroke, myocardial infarction, or peripheral artery disease. Such knowledge could inform individuals with poor collateral capacity to adopt a lifestyle that can help reduce their chances of getting diseases that could further lower their number of collateral vessels.

"If you've got a good number of these natural bypass vessels, you have something of an 'insurance policy' that favors you suffering less severe consequences if you get atherosclerosis or thrombotic disease" said senior study author James E. Faber, Ph.D., professor of cell and molecular physiology at UNC.

"And if you were born with very few, the last thing you would want to do is subject yourself to environmental factors that might further cut down the number of these vessels." Faber also is a member of the McAllister Heart Institute at UNC. Earlier this year, his team reported that these vessels form early in life and that genetic background has a major impact on how many you end up with.

The factors that put people at risk for developing stroke, heart attack, or peripheral artery disease include the usual suspects -- smoking, diabetes, hypertension, high cholesterol, family history, age. But until recently, researchers didn't know what linked those risk factors together, when it comes to insufficiency of the collateral circulation.

Faber says studies have shown that all of these factors cause the endothelial cells that line our blood vessels to produce less nitric oxide, a "wonder molecule" that protects our vasculature from disease. Now, he says, his group's findings indicate that this molecule is also a critical factor maintaining the health of the collateral circulation.

So Faber and lead study author Xuming Dai, M.D., Ph.D., of UNC's departments of medicine and physiology, wondered whether collateral vessels would be lost if the levels of nitric oxide were suppressed. They counted the number of these vessels in the brains of mice genetically engineered to lack the enzyme – called eNOS -- that makes most of the nitric oxide in blood vessel walls.

The researchers found that from the ages of three months to six months (equivalent to about twenty-one to forty-five years of age in humans) there was a 25 percent reduction in the number of collateral vessels in the mutant mice as compared to normal ones. They also saw the same percentage decrease in collateral vessels supplying the legs, where they were trying to model peripheral artery disease.

Next, the investigators wanted to know if a lack of nitric oxide would affect the way that existing collaterals respond to an obstruction in a main artery.

By blocking an artery in the legs of these genetically engineered mice, Faber and Dai were able to reroute circulation through the collateral vessels. Over a period of 2-3 weeks, the flow of detoured blood usually causes the little collaterals to enlarge their diameters by 3 to 4 fold through a process called collateral remodeling. But the researchers found that such remodeling was impaired in the mutant mice that produced less nitric oxide when compared to their normal counterparts.

In the first such experiment of its kind, Dai then succeeded in surgically removing these tiny collaterals from the mice and scanned their entire genomes for differences between the mutant and normal rodents that might explain this variation in remodeling.

"The only category of genes that was dramatically different between the two was the cell cycle control genes, genes that are involved in the proliferation of cells in the vascular wall—a process that's required for collaterals to remodel," said Dai, a clinical cardiology fellow receiving basic science training in Faber's laboratory. "This is an important function of eNOS that had not been discovered before."

Faber says that possessing a variant form of the eNOS gene that results in loss of collaterals may be one more item on the list of risk factors for cardiovascular disease. There is already evidence that healthy people may vary up to ten-fold in the abundance of their collateral circulation, so the trick may be figuring out a way to upgrade that back-up plan for those who are lacking.

"If we can figure out how these unique vessels are made and maintained in healthy tissues, we hope we can then uncover how to induce them to be made with treatments in patients who don't have enough," Faber said.

The UNC research was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

Les Lang | EurekAlert!
Further information:
http://www.unc.edu

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>