Maternal malnutrition during pregnancy could provide clue to offspring heart disease

NIH funded study of sheep shows fetal blood vessel control diminished

Based on a study of fetal sheep, scientists funded by the National Institutes of Health believe they may have found a clue to the heightened risk of heart disease seen in people who were born at low birthweight to mothers malnourished during pregnancy. The finding one day may lead to new ways to treat or even prevent heart disease in this group of people.

The researchers have learned that an important biological pathway appears to be disabled by poor nutrition during pregnancy. A biological pathway is a series of actions among molecules in a cell that leads to a certain product or a change in a cell. This pathway is involved in the dilation, or widening, of blood vessels that respond to an increased need for oxygen, such as after physical exertion. Many previous studies—of animals as well as many human beings born at low birth weight— have shown that the ability of blood vessels to dilate is reduced among individuals who did not receive enough nutrition in the womb. In these individuals, blood vessels will contract readily, but are much less likely to dilate properly.

The pathway is believed to be triggered by an as yet unidentified molecule or molecules known as endothelium-derived hyperpolarizing factors (EDHF). The researchers referred to the pathway they identified in their study as the EDHF-like pathway. Another important pathway is set in motion by nitric oxide. (The two are among several essential pathways needed for blood vessel dilation.)

In the undernourished fetal lambs that the researchers studied, the EDHF-like pathway no longer functions, leaving the nitric oxide pathway to begin the process of blood vessel dilation.

The study, conducted by researchers at North Dakota State University in Fargo, was published recently in the American Journal of Physiology: Heart and Circulatory Physiology.

“We believe we have uncovered an extremely promising lead,” said the study’s first author, Praveen Shukla, PhD, a postdoctoral researcher in the Department of Medicine, Division of Cardiology at Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine.

“If future research confirms that this pathway also has been disabled in human beings born at low birth weight, it may one day be possible to develop drug therapies to compensate for the loss of the EDHF-like pathway, or even to restore it,” stated Dr. Stephen O'Rourke of North Dakota State University, who directed the research project.


About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s website at

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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