The role of the neuroimmune axis as a new frontier in atherosclerosis

Comment on ‘Neuroimmune cardiovascular interfaces control atherosclerosis', published in Nature (https://doi.org/10.1038/s41586-022-04673-6). Atherosclerosis is an inflammatory disease,2,3 and therapeutic strategies targeting inflammation have been shown effective in reducing the incidence of adverse cardiovascular events.4 An imbalance between pro-inflammatory and anti-inflammatory processes, involving both innate and adaptive immune responses, drives chronic inflammation in the arterial vessel wall and determines the fate of the atherosclerotic plaque, from its development to its progression and instability (e.g. plaque rupture and erosion).5 Yet, the complexity of the immune responses in atherosclerosis makes any progress in this field exceptionally challenging. So far, it had traditionally been accepted that the nervous system was not involved in the pathogenesis of atherosclerosis, as plaques are not innervated.6 In the study recently published in Nature,1 Mohanta et al. found that the adventitia of arteries affected by atherosclerosis is innervated by sensory and sympathetic fibres in Apoe–/– mice and that aggregates of immune cells infiltrate these sites, forming NCIs. Their findings suggest that plaque-induced activation of sensory fibres may drive neural remodelling in the brain, which in turn may stimulate new growth of sympathetic ad parasympathetic projections in the arterial adventitia, promoting further plaque growth.