REVIEW article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1619338
This article is part of the Research TopicExploring Heart-Brain Interactions: Autonomic Imbalance and Neuromodulation Strategies in Cardiovascular DiseaseView all 3 articles
Neuro-Immune Axis in Atherosclerosis: Mechanisms of Regulation and Therapeutic Opportunities
Provisionally accepted
- 1Zhejiang Hospital, Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou, Jiangsu Province, China
- 2First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
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Atherosclerosis, the leading cause of cardiovascular morbidity and mortality worldwide, is now firmly established as a chronic immune-mediated disorder rather than a purely lipid-storage disease. Accumulating evidence has uncovered a previously underappreciated dimension of atherogenesis: the dynamic and bidirectional crosstalk between the nervous and immune systems. This neuroimmune axis, involving intricate communication between autonomic neural circuits and vascular immune cells, plays a central role in regulating arterial inflammation and plaque development. In particular, neuroimmune cardiovascular interfaces (NICIs)—specialized anatomical and functional hubs—have This is a provisional file, not the final typeset article emerged as key sites for signal integration. Here, we review recent mechanistic insights into how sympathetic and parasympathetic pathways influence immune responses in atherosclerotic vessels and hematopoietic organs. We focus on the roles of neuromodulators such as pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and galanin in shaping myeloid cell behavior, vascular tone, and endothelial activation. Additionally, we examine translational advances in neuromodulatory interventions—ranging from vagus nerve stimulation (VNS) to selective α7 nicotinic acetylcholine receptor (α7nAChR) agonists—that target these pathways to mitigate vascular inflammation in experimental models. These findings suggest that spatially resolved and temporally dynamic neuroimmune interactions constitute a critical layer of regulation in atherogenesis, offering a compelling framework for novel anti-inflammatory therapies beyond traditional lipid-lowering strategies.
Keywords: Atherosclerosis, immune, Nervous System, Mechanism, therapy
Received: 28 Apr 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Shang, Pan, Xie, Zhao, Mao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tingting Chen, Zhejiang Hospital, Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, Hangzhou, Jiangsu Province, China
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