383 Symptomatic Carotid Disease is Driven by Key Intravascular Proteins Associated With Inflammatory and Immune Cell Trafficking Across the Endothelium

INTRODUCTION: Inflammation is a major process that drives the development and augmentation of atherosclerotic disease, but the specific inflammatory markers and the mechanisms contributing to symptomatic carotid stenosis remain unclear. METHODS: Arterial blood and carotid plaque were collected from patients with both symptomatic carotid disease and other non-atherosclerotic neurovascular pathologies. Olink proteomics (Boston, MA) were used to assess expression of 184 proteins using a proximity extension assay. Peripheral arterial blood samples of patients with symptomatic carotid stenosis (n=8) were compared to the expression of various inflammatory mediators to that of age- and BMI-matched control patients (n=16) with other non-atherosclerotic neurovascular conditions (aneurysms, AVM, AVF). RESULTS: Patients with symptomatic carotid stenosis had significantly higher expression of chemotactic factors CCL23 (p<0.01) and CCL7 (p<0.05), which increase inflammatory cell trafficking and upregulation of pro-inflammatory cytokines. Consequently, increased expression of adhesion molecules, specifically ICAM-1 (p<0.01), ICAM-3 (p<0.05), VCAM-1 (p<0.05), and CDH-1 (p<0.01), was found in this group, which corroborates current evidence that these molecules directly contribute to inflammation within the blood vessel wall by mediating leukocyte migration across the endothelium and the T-cell immune response. IL-18 (p=0.0533), a potent pro-inflammatory cytokine that is known to play a major role in atherosclerotic plaque destabilization, was also upregulated in our analysis, though it did not reach statistical significance. CONCLUSIONS: The expression of pro-inflammatory mediators ICAM-1, ICAM-3, VCAM-1, CDH-1, CCL23, CCL7, and IL-18 was found to be elevated in patients with symptomatic carotid artery stenosis. This identifies a pathway, triggered by symptomatic atherosclerosis, involving a robust inflammatory and immune response across the endothelium.