THAT TIME FORGOT
Researchers link pollutant and cardiovascular disease
By GARY JAHRIG
It didn’t take Melisa Bunderson long to set her sights on a research project after arriving on the UM campus several years ago.
Bunderson, a graduate student in pharmaceutical sciences, already had earned a master’s degree in toxicology from Utah State University. And concerns over the elevated levels of arsenic in the Clark Fork River at nearby Milltown Dam were at the top of the list of community concerns when she arrived in Missoula.
The idea of furthering her education by exploring a topic of great local interest appealed to Bunderson. So she put together a proposal to conduct a study of the effects of long-term exposure to arsenic in drinking water and its relation to cardiovascular disease.
"I became intrigued by looking through papers and seeing arsenic linked to cancer, but not much to cardiovascular disease," Bunderson says. ""I was a little amazed there weren't many people trying to figure out that link."
Bunderson approached UM Center for Environmental Health Sciences researchers Howard Beall and Doug Coffin with her idea. Beall, an associate professor of toxicology, and Coffin, an associate professor of molecular genetics, signed on to the project and the research was under way.
"This was Melisa's idea. It just happened to come up at the same time the Milltown situation became newsworthy," Beall says. "We began looking into the topic and found there is a relationship between drinking water with arsenic in it and cardiovascular disease."
Beall, the principal investigator on the project, says the topic was a natural one for the center — part of UM's School of Pharmacy and Allied Health Sciences — to take on. Under the direction of Andrij Holian, the center conducts research into a number of environmental health concerns.
In taking on the project, all three members of the research team — Beall, Coffin and Bunderson — brought different types of expertise to the research lab.
was interested in metals. My general area of research is
And work well they have.
The UM team's publication of its initial research findings — that arsenic exposure increases levels of specific factors that can cause cardiovascular disease — coincided with the U.S. Environmental Protection Agency's decision to tighten restrictions on arsenic in drinking water.
The EPA also issued warnings that too much arsenic intake can contribute to cardiovascular disease, cancer and other diseases.
"We're pleased the EPA made levels of arsenic in drinking water more strict," Beall says. "Since environmental arsenic is normally found in combination with metals, we also want to look at the effect of those combinations on cardiovascular disease."
Poison for the Heart
Coffin, a five-year UM faculty member, says his team's research specifically focused on linking arsenic with atherosclerosis or coronary artery disease — the buildup of plaque within arteries connected to the heart.
"Atherosclerosis is the most important factor in the development of other heart diseases," says Coffin. "There are a lot of theories about how atherosclerosis happens. We wanted to find out if arsenic exposure is a risk factor like being overweight or smoking. We wanted to know if arsenic exposure should be treated as another risk factor."
first part of the study involved testing endothelial
cells, which line the inside of
"We exposed the cells to arsenic," Beall says. "We looked for inflammatory markers — things that lead to inflammation. We found evidence of those markers."
The UM team then moved on to testing laboratory mice. Since mice don't get atherosclerosis, Beall says, their genes are altered to model human coronary artery disease.
"There are no human studies. We have to rely on animals," he says. Some mice are continuously exposed to arsenic in drinking water at a level higher than humans generally are exposed. Others are not exposed at all. The researchers then compare the findings from the two groups.
"The main finding and most exciting is the size of the plaques in arsenic-treated mice is much more advanced than the size of the plaques in the control mice," Beall says. "This is the first controlled study showing that arsenic in drinking water in any animal model causes increases in atherosclerosis."
Coffin says data from the study will be used to look at how atherosclerosis affects overall cardiovascular fitness.
"We want to show that exposure to arsenic is likely to be a risk factor for heart disease," he says. "We want to show there are links between the cell study and the animal study."
Grant Funds Human Health
"Our overall goal is health-related," Beall says. "Our goal is to find a way to prevent and treat arsenic-induced cardiovascular problems."
who oversees the COBRE program at UM, says research
such as that being
"First is the obvious health information that is highly relevant to all of us on the cardiovascular effects of arsenic in our waterways," Holian says. "Second is the resources that this project will bring in to the University community that has a positive impact for all.
third is the synergism that is created by all working on arsenic and
related projects that will allow greater national recognition of the
strong emphasis on research that this
Beall says the grant money is paying for a lab technician, two undergraduate students and two graduate students to work on the project. And that's a plus for grad students like Bunderson who have the opportunity to work on cutting-edge research projects as part of their studies.
"This is a huge benefit to graduate students," Bunderson says. "This means we get to leave the program with some really strong research ties. That's very valuable."