DOI: 10.5061/dryad.9zw3r22tp
title: Temporal effects of sympathetic denervation on aortic remodeling and rupture in experimental abdominal aortic aneurysm

description: Abdominal aortic aneurysm (AAA) is a life-threatening condition with no
 effective pharmacologic therapies, and increasing evidence suggests that
 the sympathetic nervous system (SNS) contributes to disease progression.
 However, the temporal effects of SNS modulation on AAA stability remain
 unclear. To investigate the impact of SNS modulation on aneurysm outcomes,
 we induced AAAs in male ApoE-/- mice via continuous subcutaneous infusion
 of angiotensin II (AngII). Using 3D light sheet microscopy, we found that
 ruptured AAAs exhibited the highest sympathetic innervation in
 experimental aneurysms. Sympathetic denervation was performed using
 intraperitoneal 6-hydroxydopamine, administered either serially (before
 and during AAA induction) or at a delayed time point (after aneurysm
 formation). Mice were monitored for mortality, and surviving animals were
 evaluated at day 28 for aortic morphology, nerve density, vascularization,
 and inflammation. Both serial and delayed denervation significantly
 reduced sympathetic nerve density, approximating normal levels. Delayed
 denervation trended towards improved survival (87%) by reducing rupture
 risk after treatment, while serial denervation prevented early ruptures
 but showed diminishing benefits after mid-point treatment. Both serial
 denervation and delayed denervation increased intima-media thickness and
 reduced aortic wall collagen content. Despite these structural changes, no
 significant differences in vascularization or macrophage infiltration were
 observed across groups. These findings demonstrate that sympathetic
 denervation influences aneurysm stability through vascular remodeling,
 independent of angiogenesis or macrophage infiltration, underscoring the
 importance of SNS modulation at specific stages of AAA progression.
description: # Temporal effects of sympathetic denervation on aortic remodeling and
 rupture in experimental abdominal aortic aneurysm Dataset DOI:
 [10.5061/dryad.9zw3r22tp](10.5061/dryad.9zw3r22tp) ## Description of the
 data and file structure AJP_Supplementary_DATA.docx: * Table S1: Key
 experimental reagents and materials. AJP_Supplementary_FIGURES.docx: *
 Figure S1: Correlational analysis of nerve fiber density to lumen diameter
 of No Denervation, Delayed Denervation, and Serial Denervation groups. *
 Figure S2: Representative immunohistochemical staining of aorta and vena
 cava after vehicle only (top left) and one week after 6-OHDA (top right).
 Representative immunohistochemical staining of mesenteric branch artery
 two weeks after 6-OHDA (bottom left) and four weeks after 6-OHDA (bottom
 right). Supplemental Video 1 – 6: 3D light sheet microscopy image stack of
 tissue-cleared aortic walls from patients undergoing elective open AAA
 repair. SMA (red) highlights aortic smooth muscle, and TH (green) marks
 sympathetic nerves. Scale bar = 1000 µm. Supplemental Video 7 – 9: 3D
 light sheet microscopy image stack of tissue-cleared aortas from
 AngII-infused ApoE-/- mice, depicting non-aneurysmal aorta, aneurysmal
 aorta, and ruptured aneurysmal aorta as seen in Figure 1B. SMA (red)
 highlights aortic smooth muscle, and TH (green) marks sympathetic nerves.
 Scale bar = 1000 µm ### Files and variables #### File:
 AJP_Supplementary_Material_FINAL.docx #### File: S1_-_Human_AAA_1_Raw.mov
 #### File: S2_-_Human_AAA_2_Raw.mov #### File: S3_-_Human_AAA_3_Raw.mov
 #### File: S4_-_Human_AAA_4_Raw.mov #### File: S5_-_Human_AAA_5_Raw.mov
 #### File: S6_-_Human_AAA_6_Raw.mov #### File:
 S7_-_Abdominal_Aorta_Normal.mov #### File:
 S8_-_Abdominal_Aorta_Aneurysm.mov #### File:
 S9_-_Abdominal_Aorta_Rupture.mov #### File:
 S10_-_Abdominal_Aorta_Rupture.mov ## Code/software Microsoft Word or
 equivalent word processing application VLC player or equivalent media
 player application ## Access information Other publicly accessible
 locations of the data: * none Data was derived from the following sources:
 * none