Neuroimmune Dynamics in Diseases of the Arterial Wall: Mechanistic Foundations and Translational Prospects

Peripheral nerves are increasingly recognized as regulators of vascular pathology, shaping arterial tone, inflammation, and structural remodeling. This review delineates how neural circuits interface with the aortic wall, considers sympathetic and sensory pathways in atherosclerosis and aneurysm pathophysiology, and discusses emerging experimental approaches and therapeutic strategies.

Autonomic and sensory neural circuits are increasingly recognized as modulators of arterial disease. In experimental atherosclerosis, neuroimmune crosstalk shapes vascular inflammation and influences plaque stability. Limited available evidence from human and experimental studies suggest increased sympathetic innervation within aneurysm tissue. In preclinical models, aneurysm remodeling was linked with sympathetic input, and interventions that reduce noradrenergic signaling via sympathetic denervation or pharmacological adrenergic blockade attenuated disease severity. Improved understanding of the role for innervation in vascular pathophysiology may open therapeutic opportunities, including neuromodulation and pharmacological interventions. Clarifying sources of heterogeneity between models and clinical data can potentially refine therapeutic targets and patient selection, and advance opportunities for precision interventions. Peripheral neural circuits are integral to vascular homeostasis in health and disease, interfacing with blood vessels and regulating their physiology. Converging human and preclinical evidence implicates sympathetic innervation in disease development, and that dampening adrenergic signaling via denervation or adrenergic blockade may mitigate disease progression. This review discusses mechanistic neuroimmune crosstalk across atherosclerosis and aneurysm biology and outlines some potential translational opportunities. Together, the advances position neurovascular crosstalk as a potentially tractable axis for disease-modifying interventions.