Graduation Date

5-2019

Document Type

Master's Thesis

Degree

Master of Science

Program

Biological Science

Program Director

Meredith Protas, PhD

First Reader

Mustafa Kamani

Second Reader

Ekaterina Kalashnikova

Abstract

Pulmonary arterial hypertension (PAH) is a rare and fatal disease that affects the pulmonary artery leading to the lungs. Patients suffering from PAH have fourteen therapies on the market to help alleviate their symptoms; all approved therapies enhance the patients’ vasodilation. However, none of the therapies effectively target the key pathological problem in the disease: vascular remodeling. Therefore, a therapy that directly targets vascular remodeling remains undiscovered and is an unmet medical need. The current study reports on the characterization of a metabolic pathway that has shown an involvement in the pathogenesis of PAH, specifically in vascular remodeling. We report on two clinical disease rat models of PAH, as well as an in-vitro analysis on the pathway dynamics. We show that the signaling molecule from this pathway stimulates human pulmonary arterial endothelial and smooth muscle cell proliferation. Additionally, in the two rat models, through RT-qPCR and immunoblotting, the pathway is significantly affected in the PAH mimicking conditions. The data from this report should aid in the development of novel, more efficacious therapeutic strategies to help suffering PAH patients.

Available for download on Monday, May 16, 2022

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