New synthetic peptides could attenuate atherosclerosis

February 12, 2021

Research over the last 20 years has shown that atherosclerosis is a chronic inflammatory condition of the arterial blood vessel wall. Soluble mediators such as cytokines and chemokines are pivotal players in this disease, promoting vascular inflammation. However, the development of anti-inflammatory therapeutics directed against such mediators that could prevent atherosclerosis has proven difficult, despite promising clinical studies in the recent past.

Previous anti-inflammatory therapeutic strategies to prevent atherosclerosis, heart attacks, strokes, rheumatoid arthritis and other inflammatory diseases have mainly been based on antibodies and small molecule drugs. The Munich-based research team has now designed and chemically synthesized short chains of amino acids - i.e. peptides - that function like a minimized soluble chemokine receptor. In animal models, these peptides can block atherosclerosis.

Researchers design a new class of peptides against atherosclerosis

Chemokines orchestrate the migration of immune cells in our bodies. They are key players in inflammatory diseases, including atherosclerosis; and this is why they are of great interest to biomedical researchers.

The peptides designed and synthesized by the Munich researchers mimic certain chemokine receptors and are able to specifically inhibit chemokine mechanisms that promote atherosclerosis, whereas chemokine mechanisms that control important physiological processes in the body are not affected - one could say they are "spared".

Previous studies have shown the effectiveness of therapeutics related to cytokines and chemokines. However, these drugs, not only interfered with the effect of these mediators on atherosclerosis, but also suppressed their beneficial effects, for example those related to the host defense against infections.

"The mini-CXCR4 mimics we have developed are able to selectively differentiate between two different chemokines that target the same receptor - in this case between the atypical chemokine MIF and the classical chemokine CXCL12. This enables them to specifically block pathways underlying atherosclerosis," explained Aphrodite Kapurniotu, Professor for Peptide Biochemistry at TUM.

Peptide therapeutics are suitable and inexpensive

"Peptide-based therapeutics are often considered less stable, as peptides may get rapidly degraded in the body by enzymes called proteases. However, we can apply various state-of-the-art approaches of peptide chemistry to improve the stability of peptides, for example by introducing unnatural amino acids into the peptide sequence" Prof. Kapurniotu added.

"So far, our approach was validated only in an animal model of atherosclerosis, but future clinical applications seem possible, in particular also due to the fact that peptide-based therapeutics are substantially less expensive than antibodies," said Prof. Jürgen Bernhagen from the Institute for Stroke and Dementia Research (ISD) at the LMU University Hospital.

Therapeutic potential for inflammation diseases

The Munich researchers view these results as a „proof-of-principle" of their approach. In fact, their findings show that concepts based on mini-chemokine-receptor mimics are feasible and suggest that this kind of concept could potentially be applied to other chemokines as well.

Thus, the new molecular concept could bear therapeutic potential for atherosclerosis and other inflammatory diseases.
-end-
More information:

This is a cooperative study by Prof. Aphrodite Kapurniotu's research group (TUM) and scientists at the Institute for Stroke and Dementia Research (ISD) of the LMU Hospital (Prof. Jürgen Bernhagen) as well as the cooperating laboratories of Prof. Christian Weber (Director of the Institute for Prophylaxis and Epidemiology of Circulatory Diseases at LMU and Spokesman of the DFG Collaborative Research Center 1123 - "Atherosclerosis"), Prof. Lars Mägdefessel and Prof. Hans-Henning Eckstein (Clinic for Vascular Surgery at TUM), Prof. Martin Dichgans (ISD, LMU Hospital), and Prof. Richard Bucala (Yale University).

TUM and LMU filed a patent for the underlying molecular concept (i.e. the novel synthetic peptides), which is marketed by BayPat.

Technical University of Munich (TUM)

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.