Heavy metals and other toxins have been linked to many human diseases, but determining exactly how they damage the body remains a mystery in many cases.
New research focusing on a relatively obscure, misunderstood protein suggests mercury's link to heart disease can be traced to activation of this enzyme, which triggers a process leading to plaque buildup in blood vessel walls.
The study examined three forms of mercury, matching its characteristics in the environment. Each form of mercury caused changes in the behavior of cells that line the blood vessel walls and that can lead to cardiovascular diseases.
The study also suggests that chelation therapy, a process that removes metals from the body, and antioxidants both show signs of suppressing this activity and might be key to reducing the damage caused by mercury, and possibly other heavy metals.
The research was published in a recent issue of the International Journal of Toxicology.
"Mercury has been implicated as a risk factor in cardiovascular disease because of environmental concerns both from contamination and the atmosphere. But no one has looked at heavy metal regulation of this enzyme," said Narasimham Parinandi, director of the lipidomics and lipid signaling laboratory at Ohio State University Medical Center and senior author of the study. "If we understand this regulation and know how to block it, we can come up with proper ways to prevent the activity."
Parinandi and colleagues focused on activation of an enzyme called phospholipase D, or PLD, in cells that line arteries in the lung. They exposed the cells to the inorganic, environmental and pharmaceutical forms of mercury, and observed that all three forms activated the enzyme.
The activation of the enzyme involves a complex sequence of events in the cell membranes that in turn releases phosphatidic acid, which can damage cells in the vessel lining , called endothelial cells , and is believed to contribute to vascular disorders.
To further test the enzyme's role in blood vessel lining damage, the scientists then showed that metal chelators and antioxidants lessen the mercury-induced activation of the enzyme in endothelial cells. This portion of the study showed that different types of mercury affect the cells in different ways.