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Research shows link between atherosclerotic plaques and central nervous system

New research shows a link between atherosclerotic plaques and the central nervous system. This hitherto unknown “circuit” involves three tissues with systemic action, the immune system, the nervous system and the cardiovascular system. This crosstalk is functional because the interference in the nervous system affects the progression of atherosclerosis, as demonstrated by experimental models. It could be a target for innovative therapies.

Composed of an accumulation of cholesterol, fibrous tissue and immune cells, plaques are the hallmark of atherosclerosis. Consequences, from heart attack to stroke to peripheral arterial occlusion disease, are the leading cause of death worldwide, with 3.9 million deaths a year in Europe alone.

Published in the journal Naturethe study involved both experimental models and human tissue, through a collaboration between IRCCS Neuromed in Pozzilli, Italy, Ludwig-Maximilians University in Munich, Germany, with key findings from Professor Andreas Habenicht and Dr. Sarajo K. Mohanta, and other scientific institutions participating in the “PLAQUEFIGHT” project, funded by the European Union.

“When there is an atherosclerotic plaque – explains Professor Daniela Carnevale, Department of Angiocardioneurology and Translational Medicine at Neuromed and Full Professor at La Sapienza University of Rome and lead author of the publication – cell aggregates immune cells also form in the outer connective tissue of the blood vessel called the adventitia.Interestingly, these aggregates bear similarities to a lymph node which, under healthy conditions, regulate our immune responses.Importantly, the connective tissue surrounding the arteries is rich in nerve fibers which, as our work has now shown, make a direct connection between the plaque and the brain. In fact, this adventitious tissue is used by the nervous system as its main conduit to reach all the organs of the body.” .

Then the researchers reconstructed the entire route of the nerve fibers, up to the central nervous system. “At this point – continues Carnevale – we could see that the signals coming from the plaque, once they reach the brain, influence the autonomic nervous system through the vagus nerve (the only part of the nervous system controlling most of our organs and viscera). functions, editor’s note) to the spleen. Here, specific immune cells are activated and enter the bloodstream, causing the plaques themselves to progress”.

This is a real circuit, defined by the authors as “ABC” or “artery-brain circuit”. Like all circuits, it can be disconnected or modulated. “We have carried out other experiments – adds the professor – by interrupting the nerve connections to the spleen. In this way, the impulses on the immune cells present in this organ are interrupted. The result of this therapeutic interruption is that the plaques in the arteries have not only slowed their growth, but stabilized making the disease less severe”.

Whereas atherosclerotic plaque stability is one of the most clinically relevant traits for assessing disease severity and that in this study, “ABC” components were also identified in isolated human arteries affected by atherosclerosis, research has a very important translational effect. potential.

“It is an absolutely new vision – says Professor Giuseppe Lembo, Head of the Department of Angiocardioneurology and Translational Medicine at Neuromed and Full Professor at La Sapienza University of Rome and main author of the publication – a vision that opens up the way to new classes and previously unforeseen therapeutic strategies.One hypothesis is to act, by specific bioelectronic devices and many other potential means, on the nerves that reach the spleen, in particular on the branch of the vagus nerve connected to the ganglion celiac disease pharmacological therapy”.

Source:

Journal reference:

Mohanta, Sask., et al. (2022) Cardiovascular neuroimmune interfaces control atherosclerosis. Nature. doi.org/10.1038/s41586-022-04673-6.