Journal Article

Neuroimmune cardiovascular interfaces control atherosclerosis

Megens, Remco T. A., Beer, Michael, Bianchini, Mariaelvy, Habenicht, Livia, Santovito, Donato, Eckstein, Hans-Henning, Weber, Christian, Li, Yuanfang, Pelisek, Jaroslav, Förstera, Benjamin, Mallat, Ziad, Carnevale, Daniela, Carnevale, Raimondo, Steffens, Sabine, Pallante, Fabio, Lu, Shu, Michel, Jean-Baptiste, Klupp, Barbara G., Bernhagen, Jürgen, Habenicht, Andreas J. R., Zhang, Chuankai, Ertürk, Ali, Mettenleiter, Thomas C., Lembo, Giuseppe, Sun, Ting, D’Agostino, Giuseppe, Nosalski, Ryszard, Zhang, Xi, Perrotta, Marialuisa, Olofsson, Peder S., Ma, Zhe, Dichgans, Martin, Mohanta, Sarajo K., Szczepaniak, Piotr, Saeed, Borhan R., Hu, Desheng, Guzik, Tomasz J., Peng, Li, Yin, Changjun, Kleemann, Robert, Stanic, Karen, Carnevale, Lorenzo

2022

Overview

Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes 1 . As plaques lack innervation, the effects of neuronal control on atherosclerosis remain unclear. However, the immune system responds to plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia) 2 , 3 , 4 , 5 – 6 . Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets 7 , 8 – 9 , we postulated that the peripheral nervous system may directly interact with diseased arteries. Unexpectedly, widespread neuroimmune cardiovascular interfaces (NICIs) arose in mouse and human atherosclerosis-diseased adventitia segments showed expanded axon networks, including growth cones at axon endings near immune cells and media smooth muscle cells. Mouse NICIs established a structural artery–brain circuit (ABC): abdominal adventitia nociceptive afferents 10 , 11 , 12 , 13 – 14 entered the central nervous system through spinal cord T 6 –T 13 dorsal root ganglia and were traced to higher brain regions, including the parabrachial and central amygdala neurons; and sympathetic efferent neurons projected from medullary and hypothalamic neurons to the adventitia through spinal intermediolateral neurons and both coeliac and sympathetic chain ganglia. Moreover, ABC peripheral nervous system components were activated: splenic sympathetic and coeliac vagus nerve activities increased in parallel to disease progression, whereas coeliac ganglionectomy led to the disintegration of adventitial NICIs, reduced disease progression and enhanced plaque stability. Thus, the peripheral nervous system uses NICIs to assemble a structural ABC, and therapeutic intervention in the ABC attenuates atherosclerosis. The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/31 / 13/51 / 14 / 14/19 / 14/69 / 38/61 / 631/250/256/2515 / 64/60 / 692/699/75/593/2100 / Abdomen / Amygdala / Animals / Arteries / Arteriosclerosis / Atherosclerosis / Atherosclerosis - prevention & control / Brain / Cardiovascular system / Central nervous system / Choreography / Circuits / Cones / Connective tissue / Connective tissues / Coronary vessels / Disease Progression / Disintegration / Dorsal root ganglia / expression / Ganglia / Ganglia, Spinal / Ganglia, Sympathetic / Gene expression / Growth cones / Heart attacks / host-defense / Humanities and Social Sciences / Hypothalamus / Immune system / Immunologi inom det medicinska området / Immunology in the Medical Area / inflammation / Innervation / Interfaces / laser-capture microdissection / Leukocytes / Lymphocytes / mechanisms / Mice / multidisciplinary / Muscles / Nervous system / Neurons / Neurons - physiology / pain / Pain perception / Peripheral nervous system / Plaque, Atherosclerotic - prevention & control / Plaques / Proteins / pseudorabies virus / receptor / Science / Science & Technology - Other Topics / Science (multidisciplinary) / Smooth muscle / Spinal cord / Spleen / Statistical analysis / t-cells / Vagus nerve / Variance analysis / Veins & arteries