Abstract 1008: Phenol-Based Denervation Induces Sustained Abdominal Aortic Remodeling

Abstract

Introduction: Aortic remodeling remains an important contributor to the pathogenesis of aortic disease, including occlusive, aneurysmal, and dissection disease states. The paucity of medical therapies has driven considerable interest in elucidating the pathogenesis of these conditions; new therapeutic targets are critically needed. Prior studies have identified sympathetic nervous system signaling (SNS) as a critical regulator of arterial wall homeostasis with potent effects on inflammation and vascular remodeling. Hypothesis: This study seeks to evaluate the impact of sustained denervation on morphology and wall homeostasis of the abdominal aorta. We hypothesized that topical phenol denervation of the rat abdominal aorta would induce sustained reduction in nerve fiber density with concomitant pathologic changes to tissue morphology. Methods: Male and female Sprague-Dawley rats (n=12), aged 3 months, underwent midline laparotomy for infrarenal aorta exposure. Chemical denervation was induced via a one-time topical application of 10% phenol (n=6), while sham controls received phosphate-buffered saline (n=6). Animals were allowed to recover and subsequently sacrificed after 6 months for analysis encompassing morphology, histology, and immunohistochemistry. Results: At 6 months post-treatment, abdominal aortas subjected to phenol denervation exhibited a significant reduction in nerve fiber density compared to sham controls (92.8 ± 20.3 fibers/mm 2 vs 170.4 ± 79.0 fibers/mm 2 , p=0.042). Denervated aortas demonstrated increased elastin fragmentation breakage scores (2.8 ± 1.1 vs 1.1 ± 0.4, p=0.0056). Phenol denervated rats also had significantly decreased expression of vascular smooth muscle proteins α-SMA (32.6 ± 3.9% vs 24.6 ± 3.3%, p=0.0034) and MYH11(14.2 ± 5.7% vs 21.6 ± 3.5%, p=0.023), as well as elevated adventitial microvascular density (58.9 ± 25.2 vessels/mm 2 vs sham control 18.5 ± 8.7 vessels/mm 2 , p=0.0040). Conclusion: Single-timepoint phenol-based chemical denervation induces sustained alterations in abdominal aortic morphology and vascular remodeling over a 6-month period. These findings underscore the potential of the SNS as a therapeutic target for aortic pathologies.