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Slowing down atherosclerosis through less inflammation: protein could protect against deposits

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Researchers now know that atherosclerosis - deposits on the inner wall of blood vessels - causes inflammatory processes in the body. These processes trigger the immune system and ultimately derail the body's defenses. Munich scientists have identified a protein that can slow down the development of atherosclerosis - it plays an essential role in controlling the immune response. In the mouse model, they were able to show that inflammatory processes were intensified when specific immune cells lacked a receptor. The receptor molecule could therefore have a protective effect.

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Research has shown that atherosclerosis results from inflammatory processes in the arterial vessel wall. In the disease, the body deposits cholesterol esters and other fats into the inner wall layer of arterial blood vessels. This causes plaques to form, which can reduce blood flow to such an extent that the oxygen supply to some organs is impaired. Cardiovascular disease caused by atherosclerosis is the leading cause of death worldwide.

B cells play an essential role in the inflammatory process of atherosclerosis. These immune cells belong to the white blood cells and are part of the acquired, or adaptive, immune response. B cells mediate both protective and damaging effects via antibodies. In other words, they can promote or inhibit atherosclerosis.

Protein could be suitable for innovative therapies

But how exactly does the body regulate which process comes into play? Researchers led by DZHK scientist Prof. Dr. Sabine Steffens from the Institute for Prophylaxis and Epidemiology of Circulatory Diseases (IPEK) have now identified a protein that is crucially involved in controlling the adaptive immune response in atherosclerosis. The scientists believe this protein could be a target for innovative therapies.

"We wanted to understand better how B cells influence atherosclerotic disease in order to prospectively develop novel B cell-targeted therapies for this life-threatening disease," Steffens says of the goals of her research project. The focus of her interest was the receptor GPR55, which transmits chemical signals from outside to inside cells.

Mice lacking receptor molecule GPR55 developed larger atherosclerotic plaques

For their study, the scientists examined mouse models of atherosclerosis. B cells of the spleen of mice produce the molecule in large quantities. If the mice were given a special diet to induce atherosclerosis, the receptor was upregulated after only one month, a relatively early stage of the disease. The mice that were unable to produce GPR55 developed larger atherosclerotic plaques than the wild type. Thus, in these mice, without GPR55, B cells were excessively activated, and inflammatory processes were promoted.

Examination of human atherosclerotic plaques showed that fewer receptors were present in unstable plaques at a high risk of causing stroke than in stable plaques. "This finding suggests that the expression of the protein changes during the disease," Steffens reported.

"Our results suggest a protective role for the B-cell GPR55 pathway in atherosclerosis, potentially suggesting relevance to human pathophysiology," Steffens says. She hopes "GPR55 could be the starting point of novel therapies." Further studies will have to show whether small molecules can be used as drugs to stimulate the formation of GPR55.

Essential parts of the study were funded by the DFG Collaborative Research Center 1123 (spokesperson: Prof. Christian Weber), which was extended for another four years only in May of this year.

Scientific contact person: Prof. Dr. Sabine Steffens, Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Poliklinik, Klinikum der Universität München, Ludwig-Maximilians-Universität München, sabine.steffens(at)med.uni-muenchen.de
R. Guillamat-Prats, D. Hering, A. Derle, M. Rami, C. Härdtner, D. Santovito, P. Rinne, L. Bindila, M. Hristov, S. Pagano, N. Vuilleumier, S. Schmid, A. Janjic, W. Enard, C, Weber, L. Maegdefessel, A. Faussner, I. Hilgendorf & S. Steffens: GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation. Nature Cardiovascular Research, DOI 10.1038/s44161-022-00155-0 

Source: Pressemitteilung der Ludwig-Maximilians-Universität München