Mercury and Cardiac Risk
by N. Parinandi, PhD, Ohio State University College of Medicine
(Scroll down for a New York Times article on this subject)
Mercury is a serious environmental heavy metal pollutant found in water, soil, and air. Consumption of contaminated fish has been shown to cause cardiovascular disorders in humans. Also, the organic mercury form, methylmercury, is a serious concern in the environment and food chain. Dental amalgams which contain mercury cause a serious threat and this topic is controversial. Recently, Thimerosal, a pharmaceutical form of mercury in vaccines and other drugs has raised a serious concern as a causative agent in autism. Nevertheless, mercury and a few other heavy metals have been implicated as risk factors in cardiovascular diseases. Consumption of fish oils containing mercury (methylmercury) has been shown to cause adverse effects on cardiovascular system in humans.
We focus our research on the cell membrane lipids and lipid signaling in vascular (blood vessel) endothelial cell homeostasis. Cell membrane is the prime and the very first target of the cell (including the vascular endothelial cell) to any insult, whether physical or chemical or biological. This is often ignored by several investigators. As a trained membrane lipidologist at the Hormel Institute of the University of Minnesota (which is the only Lipid Institute in the country and often called as the Mecca of Lipids), I have focused on how several toxicants and regulators affect the cell function and viability through the dynamics of cell membrane lipids. Lipids (phospholipids containing fatty acids) constitute the major portion of the cell membranes. These membrane lipids are regulated both at the structure and function by a cascade of lipid-metabolizing enzymes called phospholipases. These phospholipases are of major 4 types: (1) Phospholipase A1, (2) Phospholipase A2, (3) Phospholipase C, and (4) Phospholipase D. All these phospholipase are important in the housekeeping of the lipid membrane architecture and function and also very crucial in cell signaling by generating bioactive lipid signals and above all pivotal in the regulation of inflammation and cell survival and function.
Virtually, there have been no reports on the action of mercury (both inorganic and organic forms) on the cell membranes of the vascular endothelial cells at the phospholipase A2 and D sites. We are one of the handful of labs in the country who focus on the regulation of phospholipase D that regulates the cell function and survival through the generation of a bioactive lipid signal mediator called “phosphatidic acid”. Therefore, we asked a question whether mercury activates phospholipase D in the vascular endothelial cells which in turn causes loss of cellular function. In fact it happened the way we predicted. Phospholipase D is activated by mercury and this enzyme plays a crucial role at the membrane site in vascular endothelial cells leading to the dysfunction of cells through oxidative stress. This was the work of Mr. Thomas Hagele (Published in the International Journal of Toxicology, The official Journal of the American College of Toxicology in Jan. 2007). Mr. Hagele is a Medical Student at the Wright State University now. This was the first report ever made on this subject. Mr. Hagele presented this work at the OSU’s Denman Undergraduate Forum and bagged the First Place (Prize) two years ago.
Secondly, we asked a question whether mercury activates phospholipase A2 in the cell membranes which in turn is responsible for the generation of inflammatory mediators in the vascular endothelial cells. Yes! Mercury caused the activation of phospholipase A2 and also induced the formation of prostaglandins (which are the prime mediators of inflammation) in the vascular endothelial cells. Also, when phospholipase A2 was blocked, the mercury-induced cytotoxicity in the vascular endothelial cells was protected. Therefore, mercury-mediated toxicity of the vascular endothelial cells is mediated by the activation of phospholipase A2 at the membrane level and is operated through the formation of inflammatory mediators such as the prostaglandins, oxidant production, and oxidation of membrane lipids. Also, our studies included the use of chelation and other protective strategies. This was done by another undergraduate student, Ms. Jessica Mazerik who is now a doctoral student at the Vanderbilt University’s Biomedicine Program. This work was published as 2 papers a couple of weeks ago: (1) in the Toxicology Methods and Mechanisms and (2) in the International Journal of Toxicology (the official Journal of American College of Toxicology). Again, these are the reports made for the first time on this subject.
These results have profound implications on not only the mercury-induced vascular endothelial cell adverse responses but also any toxicant-mediated vascular endothelial cell abnormalities which could lead to the cardiovascular risk. Vascular endothelial cell plays a major role in the regulation of blood vessel structure and function. We are currently working on the mechanisms of vascular endothelial dysfunctions caused by mercury and other toxic substances (e.g. environmental toxicants such as particulate matter and cadmium and endotoxins) through the activation of the membrane phospholipases.
Again, from our experimental findings, we believe that the cell membranes are the “Gateway of the Cells”. The first attack by a toxic substance should happen at the cell membrane. Cell membrane phospholipids and their enzymes (phospholipases) play a pivotal role in the toxicity of these toxicants. Vascular endothelial cells are no exception to this phenomenon and are very important in the environmental cardiovascular disorders/diseases.
Parinandi, Ph.D.
Assistant Professor
Lipid Signaling & Lipidomics and Vasculotoxicity Laboratory
Davis Heart & Lung Research Institute
The Ohio State University College of Medicine
Studies Link Other Ills to Mercury, Too
New York Times
by MARIAN BURROS
Published: January 23, 2008
In the past few years, several studies have concluded that elevated mercury levels may be associated not only with neurological problems but with cardiovascular disease among adults as well.
One of the studies, reported by Dr. Eliseo Guallar, an associate professor of epidemiology at the Johns Hopkins School of Public Health, in 2002 in The New England Journal of Medicine, looked at men in European countries and Israel. The mercury levels among men who had had a heart attack were 15 percent higher than those who had not.
In 2006, a National Academy of Sciences Institute of Medicine report titled ÒSeafood Choices: Balancing Benefits and Risks acknowledged some of these findings, saying that Òincreased methylmercury exposure might be a risk factor for adult cardiovascular toxicity.
The report added, for child neurodevelopment and adult cardiovascular health, emerging evidence suggests that the health benefits of seafood consumption are greater among individuals whose body burden of methylmercury is lower.
Other studies have concluded that the benefits of consuming fish, because it contains omega-3 fatty acids that may help prevent heart disease, may outweigh the risks of mercury contamination. Dr. Dariush Mozaffarian, a cardiologist and assistant professor of medicine and epidemiology at Harvard Medical School, said that the evidence is inconsistent that high mercury level has any effect on the risk of cardiovascular death among adults. More research had to be done, Dr. Mozaffarian said.
But some researchers who have examined the links between mercury and cardiovascular disease agree with Dr. Ellen Silbergeld, professor of environmental health sciences and epidemiology at Johns Hopkins School of Public Health, who said the existing evidence is strong and striking, even though more studies were needed.
It is very unwise to wait until we have complete scientific truth, said Dr. Philippe Grandjean, adjunct professor of environmental health at the Harvard School of Public Health and chairman of the department of environmental medicine at the University of Southern Denmark. The prudent judgment is to protect human health.
There is also recent epidemiological evidence on the relationship between mercury and neurological problems. One study, published in Environmental Health in 2003, linked low-level methylmercury exposure with impaired dexterity and concentration. The greater the mercury level, the greater the effect, the researchers found. The study also suggested that adults exposed to methylmercury might be at risk for vision loss and numbness of fingers and toes as well as blood pressure and fertility problems.
Increasing numbers of physicians are reporting on signs of mercury poisoning among patients who eat large quantities of fish.
Dr. Jane Hightower, a clinician and diagnostician in San Francisco, evaluated more than 100 patients who had vague, unexplained symptoms. Of them, 89 percent had mercury in their blood that exceeded the level considered acceptable by the Environmental Protection Agency.
The symptoms included memory lapses, hair loss, fatigue, sleeplessness, tremors, headaches, muscle and joint pain, trouble thinking, gastrointestinal disturbances and an inability to do complex tasks.
Dr. Hightower tracked 67 of the patients, directing them to stop eating all fish. After 41 weeks, all but two had blood mercury levels lower than the level considered acceptable. Her clinical observations, published in 2003 in Environmental Health Perspectives, indicate that such neurological problems in otherwise healthy adults recede when blood mercury levels go down.
No one is recommending that people stop eating fish, unless their blood mercury levels are dangerously high. In fact, health professionals and researchers encourage eating seafood selectively, choosing species, like salmon and sardines, that have high omega-3 fatty acids and low levels of mercury.
Fish in the diet is not an all-or-nothing story, Dr. Silbergeld said. The trick is to figure out which ones to eat.
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