Mechanistic insights and potential therapeutic interventions in aortic valve stenosis and atherosclerosis in a rabbit model

Atherosclerosis remains one of the leading causes of cardiovascular morbidity and mortality despite advances in pharmacological and interventional therapies. Even under optimal guideline-directed treatment, many patients continue to experience disease progression and recurrent cardiovascular events, highlighting the need for novel disease-modifying strategies.Accumulating evidence indicates that sympathetic nerve fibers surrounding arteries actively modulate vascular inflammation, immune cell recruitment, and plaque development. Neurovascular interfaces influence endothelial function, smooth muscle cell behavior, and inflammatory signaling, thereby contributing to plaque growth and destabilization. While increased sympathetic activity has been associated with enhanced atherosclerotic burden, experimental denervation has yielded inconsistent results, suggesting a complex and context-dependent role of the sympathetic nervous system in vascular disease.In vitro and computational models allow investigation of isolated mechanisms but fail to capture the integrated interactions between sympathetic nerves, the vascular wall, immune responses, and systemic metabolic factors that drive atherosclerosis in vivo. Moreover, human tissue samples are typically obtained at late disease stages and do not permit controlled investigation of causal relationships or longitudinal disease dynamics.The present study aims to investigate whether a catheter-based peri-arterial sympathetic denervation can attenuate plaque progression, reduce plaque volume, and promote a more stable plaque phenotype in an established rabbit model of diet- and injury-induced atherosclerosis. By enabling intra-individual comparison between denervated and sham-treated arteries within the same animal, this model minimizes biological variability and animal numbers while providing high translational relevance. The results are expected to provide mechanistic insights into neurovascular regulation of atherosclerosis and to inform the development of innovative therapeutic strategies targeting sympathetic-vascular interactions.