Protective mechanism against atherosclerosis discovered

June 13, 2018, CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Immunofluorescent staining of aortic root plaques (red) in mice lacking the gene for TACI in myeloid cells (adapted from Tsiantoulas et al., Circulation, 2018) Credit: Adapted from Tsiantoulas et al., Circulation, (2018)

Immune cells promoting inflammation play a crucial role in the development of atherosclerosis. Scientists at CeMM and the Medical University of Vienna in collaboration with the University of Cambridge showed that a survival factor for those cells also has anti-inflammatory functions and a protective role in atherosclerosis. The study, published in Circulation, provides valuable new insight for atherosclerosis research and suggests a hitherto unknown, inherited risk factor for atherosclerosis.

Atherosclerosis, the pathological narrowing of blood vessels, is the underlying cause for the majority of strokes and heart attacks, the major causes of mortality worldwide, according to the WHO. For the development of , a special type of called B2 lymphocytes are believed to play a crucial role. For their survival, they need the molecule BAFF. It has been shown that deletion or blockade of the BAFF receptors at the surface of B2 lymphocytes reduces the development of atherosclerosis in mice. Hence, a similar effect was expected when BAFF is directly targeted.

With highly specific antibodies, BAFF can be bound and neutralized. Those antibodies were tested for their effects on the development of atherosclerosis in mice by scientists from CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Medical University of Vienna in collaboration with the University of Cambridge. The results were surprising: Instead of reducing atherosclerotic lesion formation in the arteries of the tested mice, the antibody treatment lead to an increased plaque size. The findings were published in Circulation.

"We were able to show that B2 lymphocytes were efficiently depleted upon anti-BAFF antibody treatment," says senior author of the study Christoph Binder, CeMM Principal Investigator and Professor for Atherosclerosis Research at the Medical University of Vienna. "Surprisingly, the plaque size increased, indicating a hitherto unknown role of the BAFF molecule in atherosclerosis. However, in further experiments, we were able to explain these findings."

The researchers found BAFF to have anti-inflammatory properties, which has a positive effect on plaque size and atherosclerosis risk. The newly discovered mechanism is triggered by an alternative BAFF receptor (TACI) on the surface of macrophages, another type of . It was shown that these induce an anti-inflammatory process. This finding may provide important implications for atherosclerosis research and prevention: For example, mutations in the gene for TACI may confer an increased cardiovascular risk.

Explore further: New theory on why more women than men develop autoimmune diseases

More information: Dimitrios Tsiantoulas et al, BAFF Neutralization Aggravates Atherosclerosis, Circulation (2018). DOI: 10.1161/CIRCULATIONAHA.117.032790

Related Stories

New theory on why more women than men develop autoimmune diseases

June 5, 2018
New findings are now being presented on possible mechanisms behind gender differences in the occurrence of rheumatism and other autoimmune diseases. The study, published in Nature Communications, can be of significance for ...

Antibody blocks inflammation, protects mice from hardened arteries and liver disease

June 6, 2018
Researchers at University of California San Diego School of Medicine discovered that they can block inflammation in mice with a naturally occurring antibody that binds oxidized phospholipids (OxPL), molecules on cell surfaces ...

Altering the appearance of macrophages to prevent atherosclerosis

February 8, 2018
It might be possible to prevent atherosclerosis by changing the appearance of macrophages, cells of the immune system that for example digest foreign substances. In her Ph.D. dissertation, Baoyan Ren examined several ways ...

Immune system important in atherosclerosis

December 19, 2017
The immune system plays an important role in the development of atherosclerosis, the underlying cause of cardiovascular diseases. Thomas van der Heijden has discovered that immunosuppressants may play a preventative role. ...

Study examines the rise of plaque in arteries

May 25, 2018
The accumulation of cholesterol plaques in artery walls can lead to atherosclerosis, or the hardening of arteries that contributes to heart attacks and strokes. In a new study, Yale researchers investigate how plaque cells ...

PCSK9 inhibitors have unexpected anti-inflammatory effects

April 6, 2018
PCSK9 inhibition is a new therapeutic strategy for atherosclerosis which is known to lower LDL cholesterol. Research from Karolinska Institutet, presented at the ESC Congress last year and now published in the Journal of ...

Recommended for you

'Smart stent' detects narrowing of arteries

June 19, 2018
For every three individuals who have had a stent implanted to keep clogged arteries open and prevent a heart attack, at least one will experience restenosis—the renewed narrowing of the artery due to plaque buildup or scarring—which ...

Marriage may protect against heart disease / stroke and associated risk of death

June 18, 2018
Marriage may protect against the development of heart disease/stroke as well as influencing who is more likely to die of it, suggests a pooled analysis of the available data, published online in the journal Heart.

Deaths from cardiac arrest are misclassified, overestimated

June 18, 2018
Forty percent of deaths attributed to cardiac arrest are not sudden or unexpected, and nearly half of the remainder are not arrhythmic—the only situation in which CPR and defibrillators are effective—according to an analysis ...

Tick-borne meat sensitivity linked to heart disease

June 15, 2018
University of Virginia School of Medicine researchers have linked sensitivity to an allergen in red meat—a sensitivity spread by tick bites—with a buildup of fatty plaque in the arteries of the heart. This buildup may ...

Tobacco aside, e-cigarette flavorings may harm blood vessels

June 14, 2018
Flavor additives used in electronic cigarettes and related tobacco products could impair blood vessel function and may be an early indicator of heart damage, according to new laboratory research in Arteriosclerosis, Thrombosis ...

The molecules that energize babies' hearts

June 14, 2018
A metabolic process that provides heart muscle with energy fails to mature in newborns with thickened heart walls, according to a Japan–Canada research team.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.