New findings on the prevention of heart attacks and strokes

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(© Image: Depositphotos)
(© Image: Depositphotos)

Blockage of arterial blood vessels caused by atherosclerosis is largely responsible for heart attacks and strokes, which are the most common causes of death worldwide. The complex mechanisms that lead to pathological changes in the arteries are not yet fully understood. An international research team led by the Medical University of Vienna and the University Hospital of Würzburg has now made important progress in understanding this disease and identified potential new approaches for early detection and therapy. The results of the study were recently published in the scientific journal "Nature Cardiovascular Research".

Researchers already know that specialised cells called macrophages are central to the development of atherosclerosis. These cells play a critical role in the formation of so-called plaques, which narrow or block the arteries and can lead to dangerous complications - above all’heart attacks and strokes. However, the exact mechanisms of how macrophages function in this process are not yet fully understood.

In the search for the solution to this puzzle, Christoph Binder and Florentina Porsch from MedUni Vienna’s Department of Laboratory Medicine, in collaboration with Clément Cochain, Alma Zernecke and Marie Piollet from the University Hospital of Würzburg, took a closer look at the protein TREM2. TREM2 (TREM = Triggering Receptor Expressed on Myeloid Cells) controls the activity of macrophages and therefore has a potential influence on the development of atherosclerosis. The study results indicate that TREM2 plays an important role in the formation of unstable plaques, which are particularly susceptible to rupture and thus increase the risk of heart attacks and strokes. By regulating the survival of so-called foam cells, which are particularly common in atherosclerotic plaques, and by promoting the degradation and removal of damaged or dying cells, TREM2 helps to limit the formation of these dangerous plaques.

Important insight into complex mechanisms

The evidence obtained in the study that the treatment of mice prone to atherosclerosis with a specific antibody against TREM2 was able to reduce the formation of these unstable plaques is particularly promising. TREM2 thus emerges as a new therapeutic target for stabilising plaques, which could prevent heart attacks and strokes. In addition, the researchers were able to establish a link between a soluble form of this protein ("sTREM2") and the progression of atherosclerosis. TREM2 could therefore not only enable new approaches for the treatment of the disease but also serve as a potential biomarker for early detection. "Our results provide an important insight into the complex mechanisms of atherosclerosis and open up new avenues for the development of effective therapies," the researchers summarise the relevance of their work in the run-up to further studies.

Publication: Nature Cardiovascular Research

TREM2 protects from atherosclerosis by limiting necrotic core formation; Marie Piollet*, Florentina Porsch*, Giuseppe Rizzo, Frederieke Kapser, Dirk J. J. Schulz, Máté G. Kiss, Kai Schlepckow, Estrella Morenas-Rodriguez, Mustafa Orkun Sen, Julius Gropper, Sourish Reddy Bandi, Sarah Schäfer, Tobias Krammer, Alexander M. Leipold, Matthias Hoke, Mária Ozsvár-Kozma, Hannah Bene¨, Martin Schillinger, Erich Minar, Melanie Roesch, Laura Göderle, Anastasiya Hladik, Sylvia Knapp, Marco Colonna, Rudolf Martini, Antoine-Emmanuel Saliba, Christian Haass, Alma Zernecke#, Christoph J. Binder# & Clément Cochain#;­’024 -00429-9
* Co-first author
# Principal investigator