This finding - published in the July 2004 issue of Developmental Cell - may lay the groundwork for discovering ways to diagnose and prevent CHD. In an accompanying article in Developmental Cell, Epstein and collaborators at the National Institutes of Health demonstrated the pathways that they have discovered are functional in diverse organisms, including fish. In the larger picture, the researchers suggest this work may be crucial in determining why blood vessels migrate to certain destinations in the body.
The researchers engineered mice with an inactivated endothelial receptor, called PlexinD1. These mice had structural cardiovascular defects involving the outflow vessels of the heart, which resembled a common form of CHD in children and caused perinatal deaths of PlexinD1 deficient mice.
The type of CHD caused by inactivation of PlexinD1 in mice has previously been attributed to abnormalities of neural crest cells, which are important in setting up the correct arrangement of tissue in a developing embryo. "With this research, we have been able to show that this form of CHD can be caused by defects within the cells that line blood vessels. This research could lead to new ways to modify the growth of blood vessels because this receptor seems to tell blood vessels in which direction they should grow," says Epstein. With this finding, researchers hope to one day be able to manipulate where blood vessels go, which may lead to the development of therapies for any disease in which the presence of blood vessels is unwanted, including diabetic retinopathy and many types of tumors.
Other Penn researchers contributing to this study are Aaron D. Gitler and Min-Min Lu. This study was funded by grants from the National Institutes of Health and the American Heart Association.
Editor's Note You may also find this news release online at www.uphs.upenn.edu/news.
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Journal
Developmental Cell