College - Author 1
College of Science and Mathematics
Department - Author 1
Biological Sciences Department
Degree Name - Author 1
BS in Biological Sciences
Date
8-2026
Primary Advisor
Trevor Cardinal, College of Engineering, Biomedical Engineering Department
Abstract/Summary
Peripheral Artery Disease (PAD) is caused by a buildup of plaque in the arteries, leading to reduced blood flow and tissue ischemia. Arteriogenesis, the formation of natural bypasses through collateral vessels, is a promising therapeutic target for PAD, but the presence of enlarged collaterals does not always result in a protective effect. This may be because arteriogenesis is associated with loss of vascular tone, or the ability to vasodilate in response to changes in tissue metabolic demand or pharmacological agents. One of the primary regulators of vascular tone is the sympathetic nervous system (SNS), the increased activity of which increases vasoconstriction. In patients with PAD, impaired regulation of blood flow could prevent tissue from receiving adequate oxygen and nutrients during increased demand, potentially leading to tissue damage or death and the need for limb amputation. Previous work in the lab successfully visualized SNS neurons in the midzone region of the gracilis muscle. However, collateralvascular tone differed between surgeons. Denervation was observed in surgeons that had low vascular tone, prompting further analysis across different inguinal fat traumatization groups to address whether reducing fat pad manipulation increases vascular function 7 days after arteriogenesis. To address this question, mice underwent unilateral femoral artery ligation with varying degrees of inguinal fat pad manipulation. Sympathetic innervation was assessed by quantifying tyrosine hydroxylase (TH) fluorescence intensity in the gracilis anterior muscle and by measuring the distance between TH-positive nerve fibers and collateral arteriole smooth muscle cells. Consistent with previous studies, operated muscles exhibited significantly reduced TH fluorescence intensity compared with sham controls, showing decreased TH production or axonal degradation. Additionally, mice subjected to fat trauma without subsequent fat removal exhibited a significantly greater distance between sympathetic nerve fibers and collateral arterioles compared with mice receiving no fat trauma, indicating increased denervation surrounding collateral vessels. Mice that underwent fat trauma followed by fat removal displayed an intermediate phenotype. Together, these findings demonstrate that adipose tissue trauma causes sympathetic denervation during arteriogenesis. Understanding the mechanisms underlying SNS denervation and reinnervation during arteriogenesis may provide insight into the regulation of vascular tone and help identify strategies to improve collateral vessel function in patients with PAD.
URL: https://digitalcommons.calpoly.edu/biosp/51