A new study in mice shows that trehalose, a type of natural sugar, may boost the ‘housekeeping’ abilities of a certain kind of immune cell, thus reducing the buildup of plaque inside the arteries.

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The new study shows that trehalose may reduce the buildup of plaque inside the aorta. Shown here is the aorta of a mouse, with the red lines depicting the aorta’s walls and the yellow section showing the macrophages removing cellular waste.
Image credit: Ismail Sergin

Atherosclerosis occurs when plaque builds up inside the body’s arteries. Plaque is made up of fatty deposits, cholesterol, and other “waste” from our cells.

The buildup of plaque can narrow the arteries and decrease their elasticity. This, in turn, can lead to a variety of cardiovascular problems, such as increased blood pressure, coronary heart disease, peripheral artery disease, and even heart attack.

Although it is not exactly known what causes atherosclerosis, there are a number of risk factors and things that we can do to lower our chances of accumulating plaque inside our arteries. Smoking, high blood pressure, and high levels of the “bad” kind of cholesterol are all known to damage the arteries, so preventing these events from occurring may keep atherosclerosis at bay.

New research adds a potential preventive factor to the list. The natural sugar trehalose may have a protective role against atherosclerosis, as this new mouse study shows.

The research, whose senior author is Babak Razani, Ph.D., an assistant professor of medicine at Washington University School of Medicine in St. Louis, MO – was published in the journal Nature Communications.

Dr. Razani and team set out to examine the possibility of boosting the activity of certain types of immune cells called macrophages, so as to treat atherosclerosis and metabolic conditions including type 2 diabetes and fatty liver disease.

Macrophages are a type of white blood cell that helps the body to fight off infection. Their name is derived from ancient Greek terminology meaning “big eater,” which is appropriate given their size and responsibilities.

These cells are the largest of the immune cells, and they specialize in “eating” unwanted particles and expelling them as cellular waste.

Macrophages can suck in excess fat, unwanted proteins, and damaged organelles, which are tiny structures inside cells. Then, these “big eaters” break down these substances, mixing them up with enzymes in a “soup” that later gets flushed out of the cell as waste.

Dr. Razani explains the link between macrophages and atherosclerosis, as well as the motivation behind the research:

“In atherosclerosis, macrophages try to fix damage to the artery by cleaning up the area, but they get overwhelmed by the inflammatory nature of the plaques. Their housekeeping process gets gummed up. So their friends rush in to try to clean up the bigger mess and also become part of the problem. A soup starts building up – dying cells, more lipids. The plaque grows and grows,” he says.

“We are interested in enhancing the ability of these immune cells, called macrophages, to degrade cellular garbage – making them super-macrophages.”

So, in an attempt to boost these cells, the researchers tried injecting mice that had been genetically modified to be prone to atherosclerosis with a type of natural sugar called trehalose.

Trehalose is an energy-providing disaccharide made up of two glucose molecules. Its use as a food additive has been approved by the United States Food and Drug Administration (FDA), and the substance is widely used across the world.

After receiving the injection, the aortic plaques of the mice that had been treated with trehalose measured 0.25 square millimeters, compared with 0.35 millimeters in the mice that did not receive the sugar. This corresponds to a decrease of approximately 30 percent in the size of the plaque.

The plaque-reducing effect was not noticed in mice that received trehalose orally or mice that were administered a different type of sugar.

In addition to testing the effects of trehalose on aortic plaque, the researchers also shed light on the mechanism responsible for this effect.

Dr. Razani and his team show how trehalose activates a molecule called TFEB, which, in turn, invades the nucleus of the macrophages, binds to its DNA, and triggers a chain reaction that ultimately gives the immune cells “superpowers.”

Trehalose is not just enhancing the housekeeping machinery that’s already there. It’s triggering the cell to make new machinery. This results in more autophagy – the cell starts a degradation fest. Is this the only way that trehalose works to enhance autophagy by macrophages? We can’t say that for sure – we’re still testing that. But is it a predominant process? Yes.”

Babak Razani, Ph.D.

The researchers continue to look into ways that trehalose could become a widely available treatment for atherosclerosis, attempting to eliminate the need for injections and make it effective as a pill.

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