Navigation Links
Study pinpoints new role of molecule in the health of body's back-up blood circulation
Date:5/25/2010

CHAPEL HILL 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). But 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 walla 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.


'/>"/>

Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert  

Related biology news :

1. Childhood obesity indicates greater risk of school absenteeism, Penn study reveals
2. A study by the MUHC and McGill University opens a new door to understanding cancer
3. Study begins to reveal clues to the cause and progression of sepsis
4. Clones on task serve greater good, evolutionary study shows
5. New study warns limited carbon market puts 20 percent of tropical forest at risk
6. New study examines how rearing environment can alter navigation
7. Study links cat disease to flame retardants in furniture and to pet food
8. New continent and species discovered in Atlantic study
9. Study shows link between alcohol consumption and hiv disease progression
10. Feeling hot, hot, hot: New study suggests ways to control fever-induced seizures
11. Study finds environmental tests help predict hospital-acquired Legionnaires disease risk
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study pinpoints new role of molecule in the health of body's back-up blood circulation
(Date:1/7/2016)... Jan. 7, 2016 This BCC Research report ... biometric technologies and devices, identifying newer markets and exploring ... types of biometric devices. Includes forecast from 2015 to ... newer markets and explore the expansion of the present ... each type of biometric technology, determine its current market ...
(Date:1/7/2016)...  A United States District Court in ... country to interpret a biometric privacy statute in a ... the photo website Shutterfly brought by the law firm Carey ... vs. SHUTTERFLY, INC.; and THISLIFE, INC ( N.D. Ill ... the Illinois Biometric Privacy Act by collecting and scanning ...
(Date:1/6/2016)... Jan. 6, 2016 Based on its ... & Sullivan recognizes MorphoTrak, LLC, a U.S. subsidiary ... Frost & Sullivan Company of the Year Award. ... technology, Morpho Wave™ , has consolidated the company,s ... biometrics market. Morpho Wave is a highly ...
Breaking Biology News(10 mins):
(Date:2/5/2016)... Australian-US drug discovery and development company, Novogen Limited (ASX:NRT; NASDAQ: ... Chairman, Mr John O,Connor , and new Deputy Chairman, ... James Garner , has also been formally appointed to the ... Iain Ross , will resume his role on the ... , has also been formally appointed to the Board as ...
(Date:2/4/2016)... Falls Church, VA (PRWEB) , ... ... ... a first-year cybersecurity conference presented by Bloomsburg University’s Digital Forensics Club, takes ... Bloomsburg, PA. The two-day event features 20+ speakers and activities such as ...
(Date:2/4/2016)... N.J. , Feb. 4, 2016 ContraVir ... focused on the development and commercialization of targeted antiviral ... CEO & Investor Conference 2016, to be held February ... Source Capital Group,s 2016 Disruptive Growth & Healthcare Conference, ... on February 10-11, 2016. James Sapirstein , ...
(Date:2/4/2016)... ... 2016 , ... Many of the engineers at FireflySci, Inc. have been manufacturing ... apart from other cuvette manufacturers is their supercharged customer service and their extensive database ... this steady flow of inside information, they have recently revamped their manufacturing techniques to ...
Breaking Biology Technology: