New insights into why the heart does not develop properly in some children

Nearly one percent of all American babies are born with a malformed heart. Heart defects are both the most common and deadly type of conbad malformation in the United States.

Malformations of the structures on the right side of the heart have been badociated with mutations of the main regulator gene Nkx2-5.

Researchers at the University of Medicine South Carolina (MUSC) report in Scientific reports that Ccdc117, a Nkx2-5 target gene that is expressed in precursor cells of the heart, produces a protein that promotes rapid cell growth. This protein helps transfer iron-sulfur compounds created in mitochondria to the enzymes responsible for DNA replication and repair. When this protein is absent, the enzymes can not synthesize the DNA or unwind it to make repairs.

"When we removed this protein, there was a substantial decrease in the rate of DNA synthesis and a very large increase in damage to DNA," says Kyu-Ho Lee, MD, Ph. D., badistant professor of pediatrics at MUSC. and main author of the article. "The net result is that without Ccdc117, the cells block in the early stages of division."

Nkx2-5 has long been thought to promote the growth and division of precursor cardiac cells, but before Lee's discovery, researchers did not know how it was.

"We have proved that there is a link between the gene Nkx2-5, a gene known to be a common cause of conbad heart disease, and this pathway of iron metabolism, also known to control cell division," Lee explains. "Cell division is a big problem in the developing heart."

Mitochondria, which bademble iron and sulfur compounds, were once considered simply the engine of the cell. We now know that they play an important role in many biological functions, including the repair and replication of DNA.

This link between Nkx2-5 and the iron metabolism pathway leads Lee to question whether changes in the lifestyle of the pregnant woman, such as increased physical activity and improved nutrition, may reduce the risk of fetal heart defects. .

Exercise can increase the number of mitochondria, thus increasing the badembly of iron-sulfur compounds needed to enhance DNA repair and replication.

"This is an unexpected discovery that opens a new path for thinking about the genetic causes of conbad heart disease," Lee said. "For the first time, this is a pathway involving iron metabolism that links the programs of cardiac control that, as we know, are deteriorating in cases of conbad heart disease." of daily cell function that can be affected by, among other things, nutrition, exercise and metabolism. "

For the moment, any link between the general health of the mother and the risk of cardiac malformation in the fetus remains hypothetical. A definitive answer will require further study.

In future studies, Lee plans to examine the biochemistry underlying this pathway and identify the types of conbad heart disease for which it is relevant.

"Our findings offer a new way of thinking about the cellular mechanisms badociated with conbad heart disease," Lee said. "Iron-sulfur clusters have been the basis of mitochondria research for decades, and we are now beginning to understand their broader implications for general cell function, and our work once again highlights the importance of this pathway."

Lee is also investigating whether expression of Ccdc117 in placental tissues plays a role in the growth of cells that connect maternal and fetal circulation.

He asks whether his absence or under-expression is related to preeclampsia, a hypertensive pregnancy disorder that threatens both mother and baby.