In addition to crystallized cholesterol, atherosclerotic plaques always contain large quantities of immune cells but, surprisingly, no bacteria or viruses. It was previously unclear just how the body’s own defense forces are called into action.Even animals that are kept in an absolutely sterile environment can suffer from “clogging” or “furring” of the arteries when their food contains high levels of cholesterol. The same relationship is found in humans. The higher the blood cholesterol level, the greater the risk of atherosclerosis and the greater the likelihood of suffering a heart attack. “We have known this for a long time”, points out researcher Dr. Eicke Latz, “but nobody understood exactly why”.
Professor Latz and fellow researchers have succeeded for the first time in identifying the molecular trigger for inflammation in large blood vessels. “We’ve found that, given a certain type of nutrition, cholesterol crystals are deposited in the arterial walls after a relatively short time”, says Dr Düwell. “These crystals are then taken up by the immune system’s scavenger cells”. This becomes the starting signal for a catastrophic chain reaction. The unhealthy food results in the accumulation of cholesterol crystals that activate an “inflammasome” complex within the scavenger cells. One of the functions of this multi-protein complex is to induce the release of inflammatory mediators. The mediators then attract more and more immune cells to the site where the problem is occurring. The growing invasion ultimately destabilizes the vessel walls – with potentially life-threatening consequences.
“Very similar processes are observed with cases of gout”, explains Professor Latz, “although that mainly occurs in the joints”. Extremely painful attacks of gout can also be triggered by an unhealthy diet. This time however, the culprit is not fat but nucleic acids from, for instance, muscle tissue (meat). The uric acid formed in the digestion process then crystallizes. These crystals can unleash a powerful inflammatory reaction.
The innate immune system forms part of the body’s own defense 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.
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.
References:
1. Eicke Latz, et al. University of Bonn
2. Image courtesy of National Heart, Lung, and Blood Institute
