Targeting the Artery-Brain Circuit in Atherosclerosis

Researchers here discuss evidence for the involvement of the nervous system in the progression of atherosclerosis, the formation of ultimately fatal fatty deposits in blood vessel walls. These atherosclerotic lesions are sites of inflammation, drawing in macrophage cells of the innate immune system that attempt to repair the injury, but become overwhelmed by cholesterol, die, and add their mass to the growing plaque. It also appears that the presence of atherosclerotic plaque activates signals that pass via the nervous system to the brain and then to the spleen. In the spleen, monocyte cells held in reserve are activated, enter the bloodstream, travel to the plaque to become macrophages, and thus make matters worse. Atherosclerosis is a good example of a normally beneficial repair system in the body, the delivery of macrophages to injuries, becoming pathological in later life, causing harm rather than helping.

New research demonstrates for the first time the existence of a connection between atherosclerotic plaques and the central nervous system, which in turn, through the spleen, it activates the immune system, further stimulating the development of the disease. This hitherto unknown "nervous circuit" could represent a target for innovative therapies.

In correspondence with an atherosclerotic plaque an aggregate of immune cells is also formed in the external wall of the blood vessel. This aggregate, called an artery tertiary lymphoid organ (ATLO) and similar to a lymph node, is rich in nerve fibers. This work has shown that through them a direct connection is established between the plaque and the brain. "We were able to see that these signals coming from the plaque, once they reach the brain, influence the autonomic nervous system through the vagus nerve until it reaches the spleen. Here there is an activation of specific cells of the immune system that enter the circulation and lead to the progression of the plaques themselves."

It is a real nervous circuit, which the authors of the research have defined as "ABC" or "artery-brain circuit". And like all circuits, it can be disconnected or modulated. "We have conducted further experiments by interrupting the nerve connections that reach the spleen. In this way, the impulses on the immune cells present in this organ have failed. The result is that the plaques present in the arteries have not only slowed growth, but have stabilized."


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