Michael S. Brown, MD, and Joseph L. Goldstein, MD, were awarded the Nobel Prize in Physiology or Medicine in 1985 for their research on cholesterol and its effects on the heart. Since that time, they have tried to stay clear of the controversies over good and bad forms of cholesterol, and continue in their collaborative effort to figure out how high levels of low-density lipoproteins or LDL lead to heart attacks.

Dr. Brown is presenting his latest research in a special symposium sponsored by The Feinstein Institute for Medical Research on May 8 at 12 noon. Dr. Brown, a Regental chair of biomedical sciences at the University of Texas Southwestern Medical Center in Dallas, will talk about the importance of lowering low-density lipoproteins to prevent heart attacks and lower the incidence of the number one killer in the nation. Cardiovascular disease is the most frequent cause of death in men over age 35 and women over age 65 in the United States. Dr. Brown is this year’s Match Distinguished Scientist, a lecture series sponsored by the Feinstein.

“Heart attacks might well disappear if people could get LDLs low enough,” said Dr. Brown. He believes that scientists already have enough knowledge about the role of LDL to dramatically reduce the rates of cardiovascular disease. In fishing villages in Japan, the rates are 25 times lower than in the U.S. The key, Brown said, is controlling LDL through diet and a better understanding of the genes that regulate LDL.

Cholesterol is a fatty substance that is critical for every cell in the body. The liver makes cholesterol and it is also found in many of the foods we eat. Cholesterol is transported in the blood carried in lipoproteins. LDLs are lipoproteins of low density that circulate in the blood. Normally, receptors on liver cells destroy the extra burden of LDL, but if there are too many LDL particles in the system it can deposit on artery walls. There is strong evidence that high LDL levels can dramatically increase the risk of heart disease, Dr. Brown said. Animals with low levels of LDL have no atherosclerosis, and raising LDL levels trigger disease. As the LDL levels rise in certain human populations, so does heart disease. Genetic mutations that impair the body’s ability to remove LDL from the plasma cause severe atherosclerosis. And finally, there have been a number of large clinical studies that show heart disease is lowered in people taking medicines to clear LDL from the body.

Diets rich in saturated fats produce high levels of LDL. If the receptors in liver cells aren’t destroying LDL efficiently, it builds up in the system. Once LDL particles deposit in the wall of the artery, the body’s immune system wages an attack to get rid of it. But the cells that come in to destroy the LDL particles end up damaging the wall. The wall thickens and the result could be a heart attack.

After two decades, the vexing question remains: Why do people who consume a high-fat, high-cholesterol diet have high LDL levels?

Dr. Brown explained that the genes for the search-and-destroy receptors in liver cells are under a tight feedback regulation system. When people eat diets rich in cholesterol, it builds up in the liver and the gene for the LDL receptor becomes less active. The result: LDL levels increase. The Texas scientists have been trying to figure out how the cells in the liver know there is too much cholesterol around. What’s more, how does it turn down the receptor?

In 1993, Dr. Brown and Dr. Goldstein discovered sterol regulatory elementary binding protein (SREBP) that works like a thermostat for cholesterol inside of the cell. If there is too much cholesterol, the gene that makes the LDL receptor is turned off. “The SREBP senses that there is too much cholesterol and lowers the thermostat,” they say. Since their initial findings, Dr. Brown and Dr. Goldstein have found that the class of cholesterol-lowering drugs called statins turns up the thermostat. With the proverbial heat on, the liver makes more receptors and LDL levels fall.

LDL receptor deficiency can also be acquired through a diet high in cholesterol. More than half of all people in the United States have levels of circulating LDL cholesterol that are above the threshold at which atherosclerosis is accelerated. What’s more, one in 500 Americans suffer an inherited defect that leads to high blood cholesterol. One in a million people are born with no LDL receptors at all. People with this inherited gene defect called familial hypercholesterolemia often have heart attacks before they even reach adulthood.

The bottom life-saving line is this: “We should all eat low cholesterol diets or take a drug that turns on this thermostat,” said Dr. Brown.

Reporters are welcome to attend the hour-long lecture that begins at noon on Thursday May 8. The lecture will be held at North Shore University Hospital’s Rust Auditorium , 300 Community Drive in Manhasset. For more information please contact Jamie Talan at 516-562-1232.