Thursday, December 9

Can we treat heart disease by inhibiting the inflammation factory?


What do diseases like gout, cancer, Alzheimer’s, atherosclerosis, diabetes, and heart attack have in common? Jo: flamasomet!

In our research, we work to understand the importance of inflammation in cardiovascular disease, the researchers write.
  • Ida Gregersen

    Researcher, Internal Medicine Research Department, Oslo Rikshospitalet University Hospital

  • Mary Belland Olsen

    Postdoctoral, Internal Medicine Research Department, Oslo Rikshospitalet University Hospital

  • Mieke Louwe

    Postdoctoral, Internal Medicine Research Department, Oslo Rikshospitalet University Hospital

Knowledge is Aftenposten’s commitment to research and science, where researchers and professionals from all over the country contribute articles.

You might think that the most important systems of the human body have been mapped and fully understood. But that is not the case. A good example of this is a system that has evolved over many millions of years and is absolutely necessary for our survival, that is, our immune system.

Understanding the immune system is critical to understanding disease and developing drugs and vaccines, but there is still much we don’t know about how it works.

Our immune system is extremely complex. New mechanisms and processes are constantly being discovered. In the last few decades, there has been a lot of research done on how the immune system can cause disease rather than be protective. We now know that a failed immune response is important contributor to the development of many diseases, both acute and chronic.

In our research, we work to understand how the immune system contributes to the development of lifestyle diseases, such as cardiovascular disease, diabetes, and obesity.

Our immune cells are powerful inflammatory plants

A relatively recently discovered device in the immune system is the inflammasome. Was described for the first time in 2002 by Swiss researchers.

To draw a picture of what the inflammasome is, one can imagine an inflammation factory where the cell is the factory premises and the inflammasome is the machinery itself.

Inflammation is found especially in immune cells, but also in many other cells, such as skin cells and fat cells. It has been shown to be involved in almost every inflammatory condition that we know of.

So what does this machinery do? Let’s say an immune cell meets a bacterium that needs to be killed. Then this inflammasome machinery within the cell will turn on and amounts of inflammatory signals will be produced.

These signals act as warning lights and trigger an inflammatory reaction in nearby cells, so they can help eliminate the invader, which in this case is bacteria.

In some cells, the production of inflammatory signals can become so strong that the entire factory, that is, the cell, goes out into the air. In the cellular world, this is a way of alerting neighbors to danger, a bit like an airplane alarm.

Inflammation is therefore a very clever tool in the fight against invaders, but a perpetual leak alarm can be taxing on nearby cells and tissues, causing damage rather than protection.

Ida Gregersen, researcher (left), Maria Belland Olsen, postdoc, and Mieke Louwe, postdoc, all in the Internal Medicine Research Department of Oslo Rikshospitalet University Hospital.

How can the inflammasome cause disease?

Because the potential of the inflammasome is so powerful, the factory must be carefully regulated. This is done by controlling production in two steps, through two “danger signals” that inform the cell that now the machinery to combat a threat (for example, a bacterium, as in the previous example must be started) ).

As a safety mechanism to prevent an unnecessary inflammatory response, both signals must be present for the inflammatory cell to be activated.

At the first signal, factory employees are instructed to prepare parts for the machine. At the second signal, the machine is assembled. Only when the machine is properly assembled can the production of ignition signals begin.

Chronic inflammation is a major contributor to many diseases, such as cardiovascular disease and cancer.

There are many different factors that can act like these two signals. As mentioned, there may be parts of bacteria or viruses, but there can also be lifestyle factors, such as high saturated fat, cigarette smoke, or stress.

If there are many signals present at the same time, it can lead to the protection mechanisms being defeated and we obtain overactive inflammation factories. This can result in chronic inflammation.

Chronic inflammation is a major contributor to many diseases, such as cardiovascular disease and cancer. These groups of diseases are the largest and deadliest in the world today.

If we want to develop better diagnoses and treatments for these diseases, it is therefore important to understand what happens when an inflammatory reaction goes from helping us to harm ourselves. One of the pieces of this puzzle is understanding inflammation.

The future treatment of heart disease?

In our research, we work to understand the importance of inflammation in cardiovascular disease. Many studies have been conducted in cell and animal models that support an important role for the inflammasome inflammatory machinery in the development of these diseases.

Several clinical studies have tested drugs that dampen the effect of the inflammasome. One of the most famous is and study called Cantos, which showed for the first time that by inhibiting the inflammatory substance interleukin 1, which is one of the main products of the inflammasome, the risk of heart attack, stroke and death is reduced.

However, the drug used in this study is very expensive and therefore cannot be used as a preventive treatment. But these results show the enormous potential of such therapy. Later, several other studies have also supported the potential to inhibit the inflammatory cell for the prevention and treatment of heart disease.

One potential danger of suppressing our immune system, as such treatment does to some extent, is that it can no longer protect us from disease. Therefore, it is extremely important that medications are as accurate as possible.

How to hit the flicker?

What makes the inflammasome research more challenging is that there is not just one inflammasome, but at least nine different ones in the human body.

None of them are the same, they are activated by different signals and therefore different drugs are needed to dampen their effect.

In the Cantos study, mentioned above, an antibody that inhibits the product of the inflammatory machinery was used. Work is now underway to test drugs that inhibit actual factory production. In this way, the drug will be able to target specific inflammatory cells and be even more precise.

Knowledge about inflammasomes is growing, and it will be exciting to continue this development further!

Based on the article:

“Targeting the inflammasome in cardiovascular disease”, Olsen et al., J Am Coll Cardiol Basic Trans Science.

References:

Martinon, F., K. Burns, and J. Tschopp, The Inflammasome: A Molecular Platform That Activates the Activation of Inflammatory Caspases and ProIL-β Processing. Molecular Cell, 2002. 10 (2): p. 417–426.

Ridker, PM, et al., Canakinumab anti-inflammatory therapy for atherosclerotic disease. New England Journal of Medicine, 2017. 377 (12): p. 1119-1131.


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