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

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

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