Congenital heart disease (CHD) is a leading cause of mortality in children worldwide. According to the American Heart Association, Congenital cardiovascular defects are present in about one percent of live births and are the most common malformations in newborns.
Researchers from the University of Pennsylvania School of Medicine have recently identified new signaling pathways that may lead to a better understanding of how this deadly disease forms. Jonathan Epstein, MD, Associate Professor of Medicine and the study's lead investigator, identified a receptor in endothelial cells (the cells that line blood vessels) that when interrupted in mice, results in CHD and defects in the growth and arrangement of blood vessels (patterning). "With the identification of this receptor, we hope to one day develop molecular medicines that will essentially steer developing blood vessels away from where they shouldn't go," said Epstein.
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.