Study Reinforces Link between Fatty Diets, Heart Disease

May 13, 2003

- Tina Hesman St. Louis Post-Dispatch

link to article

ST. LOUIS - Researchers at Washington University have uncovered one mysterious link between high-fat diets, inflammation and heart disease.

Their study, done in mice, may have implications for Atkins dieters and people who take aspirin to prevent heart disease.

The researchers, led by Dr. Clay F. Semenkovich, studied mice that are prone to heart disease to learn how a blood-clotting protein links high fat diets and inflammation and leads to heart disease. The results of the study will appear this week in the online version of the Proceedings of National Academy of Sciences.

The scientists wanted to know why a class of powerful drugs given to people having heart attacks killed some patients when given long-term. The drugs block a protein called beta-3 integrin, which coats the surface of blood platelets. The protein helps the platelets stick together. That function is important for controlling bleeding, but sometimes sticky platelets form blood clots that may block arteries and lead to a heart attack.

The drugs don't break up existing clots, but keep new ones from forming. That helps people who are having heart attacks or heart procedures avoid further damage. Some doctors reasoned that might also help prevent blood clots from forming in the first place. But when doctors gave the drug as a preventive medicine, some of the patients died. No one knew why.

The new study suggests that high-fat diets may inhibit the beta-3 integrin protein, causing inflammation, which then leads to clogged arteries and heart disease. The researchers discovered the link when they removed the gene that produces beta-3 integrin from mice already prone to heart disease. "Knocking out" the gene in mice should produce the same effect as giving the drug long-term.

The scientists thought that the mice would be protected from heart disease because their blood would not clot as easily as in normal mice. But when the mice ate a high-fat diet - about 40 percent of the calories came from fat - "they keeled over dead and had the heart disease," Semenkovich said.

The mice died because of severe lung inflammation, but even those that survived had blocked arteries. Mice that were fed mouse chow, which contains very little fat, didn't have the same heart or lung problems.

The researchers suspect that the reason the mice still developed clogged arteries is that beta-3 integrin also helps hold blood vessels together. Removing the protein loosens the connections between cells in the blood vessel walls, providing places for platelets, cholesterol and other harmful molecules to latch onto the vessel and cause damage. The body responds with a flood of chemicals that cause inflammation, producing further damage.

The study may shed light on why some people don't respond to treatment with aspirin for the prevention of heart disease, said Dr. Jerome D. Cohen, a cardiologist who specializes in preventative medicine at St. Louis University. Aspirin helps prevent blood clots and reduce inflammation. Understanding the link between blood clotting, inflammation and heart disease may one day help doctors identify patients that may benefit from aspirin treatment and devise new therapies for those who don't, he said.

Cohen called the study "exciting" because "it may cobble together several different reasons of how our most common killer - heart disease - comes about." The study reinforces the link between high-fat diets, inflammation and heart disease, he said. "This may give us a clue to why some people may be susceptible to dietary indiscretions while others are not," Cohen said.

Semenkovich acknowledges that research in mice and other animals isn't always applicable for humans but contends that his mice are a good model for clogged arteries and heart disease.

"Some people will say `Well, mice are not men,' which is certainly true, but the blockages that occurs in these mice after eating a high fat diet is very similar to the blockages that men and women get," he said.

He cautioned against diets, such as the Atkins diet, which are laden with fat and cholesterol, even though they seem to help some people lose weight quickly.

"The fact that something works for a brief period of time does not mean it will work for a long period of time," Semenkovich said. "A good rule is moderation in all things."

---


(c) 2003, St. Louis Post-Dispatch. Distributed by Knight Ridder/Tribune News Service.