Date of Award

12-2017

Degree Name

MS in Biomedical Engineering

Department/Program

Biomedical and General Engineering

Advisor

Trevor Ryan Cardinal

Abstract

Clinical evidence indicates a higher incidence of peripheral arterial occlusive disease and associated likelihood of critical limb ischemia in women, as well as worse prognosis and decreased survival post myocardial infarction. Therefore, understanding the possible differences in underlying vascular compensation mechanisms is crucial. With arterial occlusions, necrosis and tissue injury can be naturally mitigated by the collateral circulation, improving patient prognosis. Previous sex-comparison studies describing differences in vascular remodeling are inconsistent. Therefore, the aim of this study was to describe the effect of arterial occlusion on collateral remodeling in healthy male and healthy reproductive-stage female mice. At 7 days following femoral artery ligation in C57Bl/6 and BALB/c mice, there were no sex-related differences in functional ambulatory recovery. There were no sex-related differences in mechanoadaption indicators in the collateral stem- vascular smooth muscle cell (VSMC) length and overlap, with the exception of longer smooth muscle cells in male C57Bl/6 mice, VSMC lengths 329 ± 19 verses 288 ± 13 μm, male and female. Collateral midzone luminal and abluminal diameters, as well as wall thicknesses were not different between sexes. As comprehensive sex-specific differences were not captured in our specific investigation of arteriogenesis, an evaluation of microvascular remodeling in the ischemic zone and collateral vasodilation would be of interest, as would evaluating arteriogenesis following oophorectomy with estrogen depletion. The determination of any underlying mechanistic sex-specific differences could be the foundation for which targeted therapeutics are developed, which will be crucial for closing the prognosis gap between men and women in the global treatment of peripheral arterial occlusive disease.

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