Peptides against atherosclerosis
An international team of researchers led by the Technical University of Munich (TUM) and the University Clinic of Ludwig Maximilian University in Munich has developed new synthetic peptides that prevent atherosclerosis in vitro, as well as in animal models.
Atherosclerosis is a chronic inflammatory vascular disease that is caused by lipids and is the main cause of strokes and heart attacks. Soluble mediators cytokines and chemokines play a key role in this disease, contributing to vascular inflammation. But the creation of tools aimed at disabling pro-inflammatory mediators that could prevent atherosclerosis has proved to be a difficult task, despite promising clinical studies conducted in the recent past.
The fact is that previously developed anti-inflammatory drugs to prevent atherosclerosis, heart attacks, strokes, rheumatoid arthritis and other inflammatory diseases were based on antibodies and low-molecular-weight drugs. A research group from Munich has developed and synthesized short chains of amino acids that function as a reduced soluble chemokine receptor. In animal models, these peptides blocked atherosclerosis.
A new class of peptides against atherosclerosis
Chemokines control the migration of immune cells in the body. They are important in the development of inflammatory diseases, including atherosclerosis; and therefore are of great interest to biomedical researchers.
Peptides developed and synthesized by Munich researchers mimic certain chemokine receptors and are able to specifically inhibit chemokine mechanisms that contribute to atherosclerosis, while other chemokine mechanisms that control important physiological processes in the body are not affected.
Previous studies have shown the effectiveness of drugs associated with cytokines and chemokines. However, they not only prevented the action of these mediators on atherosclerosis, but also suppressed their beneficial effects, including those associated with protecting the body from infections.
The mini-CXCR4 chemokine receptor simulators synthesized in this study are able to distinguish between two chemokines targeting the same receptor – the macrophage migration inhibition factor (MIF) and the CXC-chemokine ligand type 12 (CXC-motif chemokine ligand-12, CXCL12). This allows them to selectively block the pathways underlying atherosclerosis.
Cheap and effective
Peptide-based drugs are considered unstable because they can be rapidly destroyed in the body by proteases. However, various modern approaches applied by researchers have helped to increase the stability of peptides. One of them is the inclusion of artificial amino acids in the peptide sequence.
The effectiveness of synthetic peptides has been confirmed on an animal model of atherosclerosis, and even now clinical use seems real, in particular, due to the fact that drugs based on peptides are much cheaper than antibodies.
Therapeutic potential against inflammatory diseases
The researchers consider the results obtained as proof of their approach. In fact, they show that a concept based on imitation of chemokine receptors is viable and can potentially be applied to other chemokines as well.
Thus, a new molecular concept can form the basis for the treatment of atherosclerosis and other chronic inflammatory diseases.
Article by C.Kontos et al. Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of TUM: Synthetic "mini" receptors block atherosclerosis.