After receiving a five-year, $2.4 million grant from the
National Institute of Environmental Health Sciences (NIEHS), two University of
Cincinnati researchers will collaborate on an investigation of gene-environment
interactions during embryonic development and their consequences in adult heart
Alvaro Puga, PhD, of the Department of Environmental Health,
and Jack Rubinstein, MD, of the Department of Internal Medicine, Division of
Cardiovascular Health and Disease, received the grant from the NIEHS, an
institute of the National Institutes of Health (NIH). They will serve as
The grant will enable them to study connections between the body’s
Ah receptor (AHR) gene, fetal exposure to dioxin and cardiovascular disease.
Using mice, they will test the hypothesis that exposure to dioxin during
pregnancy redirects AHR functions toward toxic and/or adaptive responses that
can lead to adult cardiovascular disease.
"The basic idea of our research is that there is a
developmental origin of heart disease,” says Puga, who has studied
environmental toxins extensively as a faculty member in the environmental
health department’s Division of Environmental Genetics and Molecular Toxicology.
He is also an associate director of UC’s Center for Environmental Genetics,
which is funded by NIEHS and housed in the environmental health department under
the direction of Shuk-mei Ho, PhD, Jacob G. Schmidlapp Professor and Chair of
Dioxins are highly toxic compounds that are byproducts of
industrial processes and are present in the environment. They are ingested into
the body orally, Puga says (through eating the meat of cows that have grazed on
dioxin-contaminated fields, for example), and stored in fat. Dioxin can be
mobilized during pregnancy when fat stores are needed, he says.
Rubinstein says researchers will use a sophisticated high-frequency
ultrasound imaging machine to study mice that have been exposed to dioxin,
beginning in the womb.
"We can actually measure the heart function and see the
structure of the heart before the litters are born,” he says. "So we’ll be able
to follow the litters from before birth all the way out after birth and into
Adds Puga: "Congenital cardiovascular malformations are the
leading cause of neonatal and infant death and a major cause of adult cardiac
insufficiency, and there’s a critical need to understand the mechanisms that
causes these diseases.
"This study will establish the role of AHR in cardiac
development and help identify gene-environment interactions that may aggravate
heart disease susceptibility.”
The collaboration between Rubinstein and Puga was initiated
by Vinicius Carreira, a graduate student in the Puga lab and a doctor of
veterinary medicine and animal pathologist, who was interested in this project
for his doctoral thesis and contacted Rubinstein with the idea.
"His involvement in the project illustrates how critically
important the role our graduate students play is in the research done in the
College of Medicine,” Puga says.