Professor Latz has recently been recruited by the University of Bonn after working ten years in basic research in the United States. Here, he heads the new Institute for Innate Immunity (Institut für Angeborene Immunität), which has a research focus on the immune mechanisms that cause inflammatory reactions. The innate immune system forms part of the body's own defence mechanism and is able to respond rapidly and directly to a number of alarm signals that appear in the tissue environment. These triggers not only include viruses, bacteria and fungi but also certain crystals and other substances that occur during infections of in stress situations. The strength of the innate immune system is that it can respond very quickly to situations that are of danger to the host. The problem, however, is that it can also overshoot the mark. This type of overreaction is also seen in the case of pneumoconioses such as the black lung, a disease which frequently affects miners. In these lung diseases, a chronic inflammatory reaction is triggered by inhaled crystals made of silicates or asbestos. The molecular mechanisms of crystal recognition are similar to those triggered by cholesterol crystals in blood vessels.
Starting point for developing new drugs
There is still a piece of the jigsaw puzzle missing which researchers need to complete the overall picture. “We don't know precisely how the cholesterol crystals activate the inflammasome”, says Professor Latz. The findings of this study however, offer some starting points for developing new drug therapies. At present, statins are widely used in therapy. Statins reduce the synthesis of endogenous – i.e. the body's self-produced cholesterol and diminish the risk of heart attack or stroke, but they cannot inhibit the absorption of cholesterol from ones diet.
Estimates by the World Health Organization put the number of people now dying from cardiovascular diseases at almost 17 million per year. This means that one in four deaths worldwide is caused by atherosclerosis.
Trans fats are made through hydrogenation, which involves bubbling hydrogen through hot vegetable oil, changing the arrangement of double bonds in the essential fatty acids in the oil and “saturating” the “unsaturated” carbon chain with hydrogen. Because double bonds are rigid, altering them can straighten or twist fat molecules into new configurations that give the fats their special qualities, such as the lower melting point of margarine that makes it creamy at room temperature.
Kummerow, 94, has spent nearly six decades studying lipid biochemistry, and is a long-time advocate for a ban on trans fats in food.
While the body can use trans fats as a source of energy for maintenance and growth, Kummerow said, trans fats interfere with the body's ability to perform certain tasks critical to good health. Because these effects are less obvious, many researchers have missed the underlying pathologies that result from a diet that includes trans fats, he said.
Trans fats displace – and cannot replace – the essential fatty acids linoleic acid (omega-6) and linolenic acid (omega-3), which the body needs for a variety of functions, including blood flow regulation. Studies have shown that trans fats also increase low-density lipoproteins (LDLs) in the blood, a factor which some believe contributes to heart disease.
Trans fats are associated with increased inflammation in the arteries. And trans fats have been found to change the composition of cell membranes, making them more leaky to calcium. Inflammation, high LDL cholesterol and calcified arteries are the signature ingredients of atherosclerosis.
Trans fats also were shown to interfere with an enzyme that converts the essential fatty acid linoleic acid into arachidonic acid, which is needed for the production of prostacyclin (a blood-flow enhancer) and thromboxane (which regulates the formation of blood clots needed for wound healing). While some in the food oil industry believed this problem could be overcome simply by adding more linoleic acid to partially hydrogenated fats, in 2007 Kummerow's team reported that extra linoleic acid did not overcome the problem.
“Trans fats inhibited the synthesis of arachidonic acid from linoleic acid, even when there was plenty of linoleic acid available,” he said.
The new study reports that in addition to interfering with the production of arachidonic acid from linoleic acid, trans fats also reduce the amount of prostacyclin needed to keep blood flowing. Thus blood clots may more easily develop, and sudden death is possible.
According to the American Heart Association, each year more than 330,000 people in the U.S. die from coronary heart disease before reaching a hospital or while in an emergency room. Most of those deaths are the result of sudden cardiac arrest, the Heart Association reports.
“This is the first time that trans fatty acids have been shown to interfere with yet another part of the blood-flow process,” Kummerow said. This study adds another piece of evidence to a long list that points to trans fats as significant contributors to heart disease, he said.
Kummerow believes the U.S. Food and Drug Administration's new requirement (begun in 2006) that trans fats be included on food labels is inadequate and misleading. Anything less than one-half gram of trans fats per serving can be listed as zero grams, Kummerow said, so people are often getting the mistaken impression that their food is trans fat-free.
“Go to the grocery store and compare the labels on the margarines,” he said. “Some of them say zero trans fat. That's not true. Anything with partially hydrogenated oils in it contains trans fat.”
“Partially hydrogenated fats can be made trans fat-free,” Kummerow said. “The industry would be helped by an FDA ban on trans fat that would save labeling costs, medical costs and lives.”