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!
Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)
The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research