Chao Calvin, Dang Caitlyn, Reddy Nidhi, Alharbi Sara, Doan Jimmy, Karthikeyan Akashraj, Applewhite Brandon, Jiang Bin
Division of Vascular Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL.
Department of Biomedical Engineering, Northwestern University McCormick School of Engineering, Evanston, IL.
JVS Vasc Sci. 2024 Mar 26;5:100202. doi: 10.1016/j.jvssci.2024.100202. eCollection 2024.
Sympathetic innervation plays a pivotal role in regulating cardiovascular health, and its dysregulation is implicated in a wide spectrum of cardiovascular diseases. This study seeks to evaluate the impact of denervation of the abdominal aorta on its morphology and wall homeostasis.
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), whereas sham controls received phosphate-buffered saline (n = 6). Animals were allowed to recover and subsequently were sacrificed after 6 months for analysis encompassing morphology, histology, and immunohistochemistry.
At 6 months post-treatment, abdominal aortas subjected to phenol denervation still exhibited a significant reduction in nerve fiber density compared with sham controls. Denervated aortas demonstrated reduced intima-media thickness, increased elastin fragmentation, decreased expression of vascular smooth muscle proteins (α-SMA and MYH11), and elevated adventitial vascular density. Sex-stratified analyses revealed additional dimorphic responses, particularly in aortic collagen and medial cellular density in female animals.
Single-timepoint phenol-based chemical denervation induces alterations in abdominal aortic morphology and vascular remodeling over a 6-month period. These findings underscore the potential of the sympathetic nervous system as a therapeutic target for aortic pathologies.
Aortic remodeling remains an important consideration in the pathogenesis of aortic disease, including occlusive, aneurysmal, and dissection disease states. The paucity of medical therapies for the treatment of aortic disease has driven considerable interest in elucidating the pathogenesis of these conditions; new therapeutic targets are critically needed. Here, we show significant remodeling after phenol-induced denervation with morphologic, histologic, and immunohistochemical features. Future investigations should integrate sympathetic dysfunction as a potential driver of pathologic aortic wall changes with additional consideration of the sympathetic nervous system as a therapeutic target.
交感神经支配在调节心血管健康方面起着关键作用，其功能失调与多种心血管疾病有关。本研究旨在评估腹主动脉去神经支配对其形态和血管壁稳态的影响。
3个月大的雄性和雌性Sprague-Dawley大鼠（N = 12）接受中线剖腹术以暴露肾下腹主动脉。通过一次性局部应用10%苯酚诱导化学去神经支配（n = 6），而假手术对照组接受磷酸盐缓冲盐水（n = 6）。让动物恢复，随后在6个月后处死进行形态学、组织学和免疫组织化学分析。
在治疗后6个月，与假手术对照组相比，接受苯酚去神经支配的腹主动脉神经纤维密度仍显著降低。去神经支配的主动脉显示内膜中层厚度减小、弹性蛋白碎片化增加、血管平滑肌蛋白（α-SMA和MYH11）表达降低以及外膜血管密度升高。按性别分层分析显示出额外的二态性反应，特别是在雌性动物的主动脉胶原蛋白和中层细胞密度方面。
基于苯酚的单次化学去神经支配在6个月期间诱导腹主动脉形态改变和血管重塑。这些发现强调了交感神经系统作为主动脉疾病治疗靶点的潜力。
主动脉重塑仍然是主动脉疾病发病机制中的一个重要考虑因素，包括闭塞性、动脉瘤性和夹层疾病状态。治疗主动脉疾病的药物疗法匮乏促使人们对阐明这些疾病的发病机制产生了浓厚兴趣；迫切需要新的治疗靶点。在这里，我们展示了苯酚诱导去神经支配后具有形态学、组织学和免疫组织化学特征的显著重塑。未来的研究应将交感神经功能障碍作为病理性主动脉壁改变的潜在驱动因素，并进一步考虑将交感神经系统作为治疗靶点。
