Neuroimmune cardiovascular interfaces control atherosclerosis

Mohanta, S. K. et al. (2022) Neuroimmune cardiovascular interfaces control atherosclerosis. Nature, 605(7908), pp. 152-159. (doi: 10.1038/s41586-022-04673-6) (PMID:35477759)

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Abstract

Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes . 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) . Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets , 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 entered the central nervous system through spinal cord T -T 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.

Item Type:Articles
Keywords:Ganglia, spinal, atherosclerosis - prevention & control, ganglia, sympathetic, disease progression, neurons - physiology, plaque, atherosclerotic - prevention & control, animals, mice.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nosalski, Mr Ryszard and Guzik, Professor Tomasz
Authors: Mohanta, S. K., Peng, L., Li, Y., Lu, S., Sun, T., Carnevale, L., Perrotta, M., Ma, Z., Förstera, B., Stanic, K., Zhang, C., Zhang, X., Szczepaniak, P., Bianchini, M., Saeed, B. R., Carnevale, R., Hu, D., Nosalski, R., Pallante, F., Beer, M., Santovito, D., Ertürk, A., Mettenleiter, T. C., Klupp, B. G., Megens, R. T. A., Steffens, S., Pelisek, J., Eckstein, H.-H., Kleemann, R., Habenicht, L., Mallat, Z., Michel, J.-B., Bernhagen, J., Dichgans, M., D'Agostino, G., Guzik, T. J., Olofsson, P. S., Yin, C., Weber, C., Lembo, G., Carnevale, D., and Habenicht, A. J. R.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Nature
Publisher:Nature Publications Group
ISSN:0028-0836
ISSN (Online):1476-4687
Published Online:27 April 2022
Copyright Holders:Copyright © 2022 The Author(s), under exclusive licence to Springer Nature Limited
First Published:First published in Nature 605(7908): 152-159
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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