Date of Completion

Spring 5-1-2018

Thesis Advisor(s)

Judy Brown

Honors Major

Allied Health Sciences

Disciplines

Biological Factors | Cardiology | Cardiovascular Diseases | Circulatory and Respiratory Physiology | Medical Molecular Biology | Medicine and Health Sciences

Abstract

Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating associated biomarkers such as high blood pressure and dyslipidemia. There is a need for medical treatments that focus on neovascularization and angiogenesis to create new microvessel networks that can effectively bypass atherosclerotic blockages. One potential candidate for peripheral artery disease management is thioredoxin-1 (Trx-1). Trx-1 is a protein that has been shown to be an upregulator of neovascularization as well as a potent anti-oxidant. The delivery of proteins for therapy must be achieved using an appropriate delivery vehicle. Exosomes may be an appropriate delivery vehicle, as a growing body of research has demonstrated their role in natural signaling processes, as well as their low immunogenic profile. This study investigates the effects of transplantation of exosomes isolated from Trx-1 overexpression mice in a mouse model of hind-limb ischemia. Mice were subjected to hind-limb ischemia, and had either Trx-1 exosomes (treatment), wild type exosomes (positive control), or phosphate buffered saline (vehicle control) injected into their semimembranosus and gastrocnemius muscles. Quantification of perfusion 28 days after induction of hind-limb ischemia revealed that Trx-1 exosome transplantation resulted in a mean perfusion ratio of 77.4%, as opposed to 38.4% in the vehicle control group. These results show that Trx-1 exosomes may be a potential target for future medical treatment of peripheral artery disease.

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