Hope for newborns found in heart’s early beginning

CORNELL (US)—Congenital heart defects are the most common malformations in newborns born in the United States, and in most cases, scientists don’t know why the defects occur. Treatment options, including valve replacement surgery, come with a host of drawbacks for tiny infants. Jonathan Butcher, assistant professor of biomedical engineering at Cornell University, studies embryonic heart valve development from the very beginning of the process with hopes that a greater understanding will lead to new treatments.

“More and more, it’s becoming apparent that many cardiac diseases and many vascular diseases are actually caused by failure of the valves,” says Butcher.

Heart valves—tiny, whisper-thin membranes often overshadowed by the complexities of the cardiovascular system—are just now being recognized for their importance, Butcher notes. His research looks at the way mechanical forces like blood pressure, blood velocity, and the stretching and contracting of the heart muscle influence embryonic heart valve development.

“The formation of the heart and its valves requires feedback from the local environment,” he says. “We think that part of the process that determines how the heart will change its shape and grow is driven by how it receives and responds to these mechanical stimuli.”

To test his theory, Butcher, who is funded in part by a Scientist Development grant from the American Heart Association, studies developing hearts in chick embryos, which are similar in key ways to human hearts.

By surgically altering the pumping embryonic heart during development—the embryo can be grown outside the shell—Butcher and colleagues are able to use ultrasound and micro CT-scan imaging to observe and quantify how changes in blood flow patterns affect subsequent cell and tissue matrix development. They also isolate heart cells from healthy chick embryos and observe their growth and behavior when subjected to similar conditions in vitro.

Providing the right stimuli means understanding the complex interactions among genetic, chemical, and mechanical factors, Butcher says; but while those factors are too numerous to test individually, computational models can offer valuable clues.

“We don’t want to make just individual components; we want to try to capitalize on the system,” he explains. “So the next step is, instead of looking at each of these factors individually, we try to look at a combinatorial approach.”

Ultimately, Butcher hopes to re-create the conditions that drive the heart to develop healthy valves from stem cells—and then to use that system to engineer replacement valves or treatments for babies with congenital defects, or for older patients whose valves deteriorate due to disease.

“Some of these developmental pathways are recapitulated in adult valve disease,” he adds, so understanding how valve tissue develops in healthy hearts could lead to new strategies for stopping or reversing deterioration.