Introduction:
The objective of this study is to understand the role of neurological factors, specifically those from the perivascular sympathetic nervous system (SNS), on the initiation and development of Abdominal Aortic Aneurysm (AAA).
Hypothesis:
We hypothesize that the formation of AAA is associated with the loss of perivascular SNS-induced vasoconstriction specific to the aneurysm region.
Methods:
We developed a rat Abdominal Aortic Denervation (AAD) model, where the infrarenal aorta of Spauge Dawley rats was denervated with surgical removal of nerve fibers and chemical denervation with 10% phenol (
Figure. A
). A sham control group was included where the infrarenal aorta was treated with PBS. The arteries were harvested at 1 month after the surgeries for histological assessment.
Results:
The denervated aortas exhibited significant thinning of the aortic wall including the media and the adventitia, compared to the sham controls (
Figure. B
). Moreover, degradation of elastin, demonstrated by the fragmentation of elastic fibers and the decreased number of lamellar units, was also observed in the dennervated aortas in comparison to the sham controls. While the control aortas were well innervated with perivascular nerve bundles adjacent to the adventitia, no nerves were found surrounding the denervated aortas, suggesting successful denervation.
Conclusions:
We generated an AAD model that could be used for mechanistic understanding and therapeutic development of AAA. The preliminary data suggest a direct link between the lack of aortic sympathetic innervation and AAA formation. Long-term studies are currently underway to further characterize changes in the aortic walls after sympathetic denervation.
Figure. (A)
Illustration of the denervated region on the rat infrarenal aorta. (
B
) Histological staining of control and denervated rat abdominal aortas at 1 month after surgery. Yellow stars: para-aortic nerve bundles. Scale bar = 200 μm.