Nav: Home

Atherosclerosis: Endogenous peptide lowers cholesterol

January 19, 2017

Cells of the innate immune system that play an important role in development of atherosclerosis contain a protein that reduces levels of cholesterol in mice - and thus helps to inhibit or mitigate the disease.

Atherosclerosis remains one of the primary causes of premature death in modern Western societies. The term itself refers to insoluble, fat-rich deposits that form on the inner wall of major blood vessels resulting in a chronic, localized inflammation. These so-called plaques obstruct blood flow and can ultimately lead to heart attacks and strokes. The unresolved inflammatory reactions that lead to atherosclerosis are initiated by immune cells in response to perturbations in lipidmetabolism owing to the presence of excess cholesterol (hypercholesterolemia) in the circulation. Researchers led by LMU's Oliver Söhnlein have now shown in mice that one of the cell types involved produces a protein that inhibits atherosclerosis by intervening in cholesterol metabolism. The new finding, reported in the journal EBioMedicine, could open up new options for the treatment of atherosclerosis.

Initiation and progression of atherosclerosis are closely linked to the activation of specific classes of cells that are part of the immune system. In earlier experiments, Söhnlein and his colleagues had shown that white blood cells called neutrophils play an important role in the process. The most abundant protein found in human neutrophils is human neutrophil peptide 1 (HNP1), which is known to have anti-microbial and pro-inflammatory functions. In contrast, mouse neutrophils normally do not express this protein at all. "This observation provided us with a unique opportunity to study the function of this protein. To do so, we genetically constructed a mouse strain that is not only prone to atherosclerosis, but also produces high levels of HNP1," Söhnlein explains. Much to their surprise, the LMU team found that the atherosclerotic lesions that formed in these mice were much smaller than those seen in the mice that lacked HNP1. "We expected to see exactly the opposite effect - in particular because we had previously discovered that HNP1 stimulates the recruitment of atherosclerosis-promoting monocytes to sites of inflammation," Söhnlein adds.

When they examined the HNP1-expressing mice more closely, the researchers discovered that the animals had lower levels of circulating cholesterol than control mice. Because cholesterol is not soluble in water, it is transported in the bloodstream in association with so-called lipoproteins. Lipoproteins are often divided into good guys and bad guys. The good guys, including HDL, transport cholesterol from the tissues to the liver and thus reduce the risk of atherosclerosis. The bad guys, like LDL, convey cholesterol in the opposite direction - from the liver to the tissues. High levels of circulating LDL thus enable more cholesterol to be delivered to endothelial cells that are especially prone to damage or are already damaged, and therefore tend to promote atherosclerosis. "Indeed, we were able to show that HNP1 binds to LDL in the bloodstream and induces rapid uptake of circulating LDL by the liver, thus reducing hypercholesterolemia," says Söhnlein. This can account for the reduction atherosclerotic lesions in HNP1-expressing mice.

The researchers believe that their findings may lead to new approaches to the treatment of hyperlipidemia. "Since HNP1 is a natural constituent of the human body, therapeutic use of the protein would be expected to be relatively free of side-effects and should not compromise immune defenses," Söhnlein points out.
-end-


Ludwig-Maximilians-Universität München

Related Immune System Articles:

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.