Protective mechanism against atherosclerosis discovered

June 12, 2018

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 atherosclerosis, a special type of white blood cells called B2 lymphocytes have been suggested 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 where 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 (DOI: 10.1161/CIRCULATIONAHA.117.032790).

"We were able to show that B2 lymphocytes were efficiently depleted upon anti-BAFF antibody treatment", senior author of the study Christoph Binder, CeMM Principal Investigator and Professor for Atherosclerosis Research at the Medical University of Vienna, describes the results of the study. "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 immune cells. It was shown that these cells 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.
-end-
The study "BAFF Neutralization Aggravates Atherosclerosis" was published in Circulation on June 5, 2018 . DOI: 10.1161/CIRCULATIONAHA.117.032790

Authors: Dimitrios Tsiantoulas#, Andrew P. Sage#, Laura Göderle, Maria Ozsvar-Kozma, Deirdre Murphy, Florentina Porsch, Gerard Pasterkamp, Jörg Menche, Pascal Schneider, Ziad Mallat# and Christoph J. Binder#. (# equal contribution)

The study was funded by the Austrian Science Fund FWF, the European Union, the British Heart Foundation and the European Research Council (ERC).

Christoph Binder obtained his MD degree at the University of Vienna in 1997 and received his Ph.D. in Molecular Pathology at the University of California San Diego (UCSD) in 2002. Following a postdoctoral training period at UCSD, he joined the Institute for Laboratory Medicine of the Medical University of Vienna and became Principal Investigator at CeMM in 2006. In 2009 he was appointed Professor of Atherosclerosis Research at the Medical University of Vienna. Christoph Binder is dually affiliated with CeMM and the Medical University of Vienna. http://cemm.at/research/groups/christoph-binder-group/

The mission of CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is to achieve maximum scientific innovation in molecular medicine to improve healthcare. At CeMM, an international and creative team of scientists and medical doctors pursues free-minded basic life science research in a large and vibrant hospital environment of outstanding medical tradition and practice. CeMM's research is based on post-genomic technologies and focuses on societally important diseases, such as immune disorders and infections, cancer and metabolic disorders. CeMM operates in a unique mode of super-cooperation, connecting biology with medicine, experiments with computation, discovery with translation, and science with society and the arts. The goal of CeMM is to pioneer the science that nurtures the precise, personalized, predictive and preventive medicine of the future. CeMM trains a modern blend of biomedical scientists and is located at the campus of the General Hospital and the Medical University of Vienna. http://www.cemm.at

For further information please contact

Mag. Wolfgang Däuble
Media Relations Manager
CeMM
Research Center for Molecular Medicine
of the Austrian Academy of Sciences
Lazarettgasse 14, AKH BT 25.3
1090 Vienna, Austria
Phone +43-1/40160-70 057
Fax +43-1/40160-970 000
wdaeuble@cemm.oeaw.ac.at
http://www.cemm.at

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

Related Atherosclerosis Articles from Brightsurf:

How hormone therapy slows progression of atherosclerosis
As one of the most common treatments for effectively managing menopause symptoms, hormone therapy (HT) is also known to provide multiple health benefits, including slowing the progression of atherosclerosis.

T cells can shift from helping to harming in atherosclerosis
At La Jolla Institute for Immunology (LJI) researchers are dedicated to finding a way to stop plaques from forming in the first place.

New nanoparticle drug combination for atherosclerosis
Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation.

Atherosclerosis -- How a microRNA protects vascular integrity
Ludwig-Maximilian-Universitaet (LMU) in Munich researchers have discovered a hitherto unknown molecular function of a specific microRNA that preserves integrity of the endothelium and reduces the risk of atherosclerosis.

Atherosclerosis progresses rapidly in healthy people from the age of 40
A CNIC study published in JACC demonstrates that atheroma plaques extend rapidly in the arteries of asymptomatic individuals aged between 40 and 50 years participating in the PESA-CNIC-Santander study.

Scaling up a nanoimmunotherapy for atherosclerosis through preclinical testing
By integrating translational imaging techniques with improvements to production methods, Tina Binderup and colleagues have scaled up a promising nanoimmunotherapy for atherosclerosis in mice, rabbits and pigs -- surmounting a major obstacle in nanomedicine.

Bladder drug linked to atherosclerosis in mice
A drug used in the treatment of overactive bladder can accelerate atheroclerosis in mice, researchers at Karolinska Institutet in Sweden report in a study published in the Proceedings of the National Academy of Sciences (PNAS).

A new therapeutic target for blocking early atherosclerosis in progeria
Researchers at the Centro Nacional de Investigaciones Cardiovasculares and the Universidad de Oviedo have discovered a new molecular mechanism involved in the premature development of atherosclerosis in mice with Hutchinson-Gilford progeria syndrome.

Protective mechanism against atherosclerosis discovered
Immune cells promoting inflammation play a crucial role in the development of atherosclerosis.

Atherosclerosis: Stopped on time
For the first time, LMU researchers are pointing out the influence of the internal clock on atherosclerosis.

Read More: Atherosclerosis News and Atherosclerosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.