01:18pm Friday 18 October 2019

UNMC research shows folic acid can reduce congenital heart defects

It has long been known that taking folic acid during pregnancy can reduce neural tube defects in newborns.
More recently, evidence has accumulated that folic acid also may reduce congenital heart defects. However, research progress has been limited, because there were few clues about the molecular or biological basis of folic acid’s effect on newborns.
Now, thanks to a University of Nebraska Medical Center research study, there is convincing evidence about the central role of a gene that regulates uptake of folic acid in cells that are the key to normal heart development.
The research originally appeared in the June issue of the journal Developmental Dynamics and was included in the Highlights section of the journal’s current August issue. In an editorial, the journal said the discovery represents “an exciting advance in developmental biology.”
According to the March of Dimes, congenital heart defects are the No. 1 birth defect. In the United States alone, more than 25,000 babies are born each year with a congenital heart defect. That translates to 1 out of every 115 to 150 births. To put those numbers into perspective, only 1 in every 800 to 1,000 babies is born with Down syndrome.
Tom Rosenquist, Ph.D., vice chancellor for research at UNMC, was the lead scientist on the study, which looked at experimental chicken embryos under a high powered microscope.
Customized gene blockers were injected into selected cells of the embryos to block a key gene that is used to make a receptor for folic acid.
At the same time, researchers injected a gene taken from a jellyfish that produces a protein that glows green under special fluorescent light. In this way, they were able to follow the fate of the treated cells, which migrate into the developing heart and are required for formation of the separate ventricles, aorta and the pulmonary artery.
The surprising result was that a brief, 24-hour disruption of the flow of folic acid into these important cells had severe, permanent consequences, Dr. Rosenquist said. The cells were never able to migrate properly, he said, resulting in abnormal heart development.
The experimental model used by Dr. Rosenquist and his colleagues has been used previously to discover many highly significant, basic aspects of heart development that were later found to be applicable to human health.
That’s why the results of the new study are significant, Dr. Rosenquist said, as they demonstrate the importance of genetic regulation of folate receptors, which grab passing folic acid and concentrate it into rapidly dividing heart-specific cells in early embryos.
The study also provides a solid scientific basis for the importance of supplemental vitamin use during even the earliest stages of development.
Since birth defects still occur in women who take folic acid, Dr. Rosenquist said that more research needs to be done to determine the optimum dose or timing of folic acid or other vitamins and how they interact with the genetic make-up of the mother and/or the baby.
He said his research team is currently studying vitamin B12 during early development to determine its value in promoting normal growth of the brain and heart.
Other UNMC people working with Dr. Rosenquist on this study included: Gregory Bennett, Ph.D., associate professor, genetics, cell biology and anatomy; Richard Finnell, Ph.D., adjunct professor, pediatrics; and Tammy Chaudoin, research technician, genetics, cell biology and anatomy.
Through world-class research and patient care, UNMC generates breakthroughs that make life better for people throughout Nebraska and beyond. Its education programs train more health professionals than any other institution in the state. Learn more at unmc.edu.

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