UNC co-authors postdoctoral researcher Joseph Kearney and graduate student Nicholas Kappas measured the efficiency of vessel formation using mouse embryonic stem cells genetically engineered to lack the flt-1 gene and then induced to become endothelial cells.
Mutant and normal embryonic stem cells were additionally engineered to express the green fluorescent protein. This "marker" allows fluorescence microscopy to visualize living cells.
The experiment enabled the researchers to analyze the dynamics of vessel formation in real time by performing time-lapse imaging of live endothelial cells. Using this method they demonstrated that blood vessels made from cells lacking the flt gene are defective in sprouting and that these sprouts migrate less quickly. These findings may have implications for future therapies.
"For instance, coronary heart disease, which is commonly treated by bypass surgery, requires reconstruction of blood vessels using veins from other parts of the body," said Bautch. "Diabetes is another pathological condition associated with loss of circulation in the limbs and extremities."
The goal of angiogenic therapy in these situations is to restore circulation non-surgically.
"There have been attempts to induce blood vessel formation by manipulating the VEGF molecular pathway. Most of the time you don't get functional vessels, but a set of dilated vessels that haven't made the right connections," said Bautch.
"We, along with others, are now beginning to unravel the complexity of this pathway. We think the flt-1 receptor actually regulates the amount of VEGFA required for proper vessel formation. So having the right amount of VEGF at the right spot and in the right context is critical," she added.
Department of biology co-authors, along with Bautch, Kearney and Kappas, were Catharin
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Contact: L.H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
15-Jun-2004