Degree Name

BS in Biomedical Engineering


Biomedical and General Engineering Department


Trevor R. Cardinal


Of the approximately 8 million Americans who suffer from ischemic peripheral arterial occlusive disease (PAOD), many present with intermittent claudication, or pain associated with exercise. Impaired vasodilation of resistance vessels is a potential explanation for this symptom. Occluded arteries can lead to increased flow through collateral vessels, which function as natural bypasses around the obstruction. This increase in blood flow and resulting shear stress can cause outward remodeling, or arteriogenesis, which improves the efficacy of collaterals. However, following femoral artery ligation in a mouse model of chronic ischemia, vasodilation in the stem region of collateral vessels is impaired at day 7. In the outwardly remodeled collateral stem, the vessel diameter increase is not associated with cell proliferation, suggesting the functionality of the present smooth muscle cells (SMCs) may account for the impaired vasodilation. A potential mechanism for increased vessel diameter in the collateral stem is mechanoadaptation of the vascular SMCs to adapt to the increased fluid shear stress as a result of the increased blood flow. Indeed, decreased SMC overlap and increased SMC length (indicators of mechanoadaptation) coincides with impaired vasodilation in the C57BL/6 mouse strain, which exhibits a large number of collateral vessels and robust collateral remodeling. Collateral density, remodeling following an ischemic event, and VEGF-A expression differ widely among mouse strains, with BALB/c mice exhibiting impaired arteriogenesis due to a polymorphism of the Vegfa gene. It is hypothesized that following femoral artery occlusion in BALB/c mice, the SMC mechanoadaptation in the profunda femoris artery will be impaired, which should normalize vasodilation, if mechanoadaptation is a cause of impaired vasodilation in the collateral stem. To test this hypothesis, the femoral artery was ligated in BALB/c mice, before maximal vasodilation at day-7 post-surgery. The animals were then perfusion fixed before resecting and immunostaining the profunda femoris artery to measure SMC length and overlap. The resting and diameters were not different at 40 3m and 48 2 m, and the maximally dilated diamters were not different at 61 4 m, and 65 3 m for the control and day-7 post-ligation profunda femoris arteries, respectively. The increase in diameter for day-7 post-ligation and control profunda femoris arteries were not different, with a percent change of 52 11% and 413%. SMC length between day-7 post-ligation and control hindlimbs was not different, at 351 26m verses 318 57m in the control. SMC overlap reduced in the day-7 post-ligation hindlimb, 18 2m versus 22 m in the control. These results indicate a subtle impairment in BALB/c collateral stem remodeling, and suggest that the cell processes involved in increasing smooth muscle cell length may impair vasodilation signaling. Further studies are necessary to evaluate the causal relationship between mechanoadaptive remodeling and impaired vasodilation.