Date of Graduation

5-2024

Document Type

Thesis

Degree Name

Bachelor of Science in Chemical Engineering

Degree Level

Undergraduate

Department

Chemical Engineering

Advisor/Mentor

Richardson, William

Committee Member/Reader

Walker, Heather

Committee Member/Second Reader

Walters, Keisha

Abstract

Heart disease the leading cause of death for both men and women in the United States. Cardiac fibrosis, or accumulation of extracellular matrix proteins in the heart, can occur after a heart attack and increase the risk for further complications. Current treatments for heart disease do not include extracellular matrix regulators, partly due to the complicated signaling network responsible for the production of these proteins. By using a computational model of the signaling network in cardia fibroblasts, the relationship between particular molecules and downstream extracellular matrix production can be examined.

Biological sex is an important factor for cardiac health and for drug development. In this study, progesterone signaling was added to a previously published signaling network model for cardiac fibroblasts. Progesterone was found to decrease the overall production of extracellular matrix proteins. Additional trials examined the effect of each of three estrogen receptors in the model, finding that estrogen receptor beta largely activates proteases, decreasing overall extracellular matrix production. Finally, a sex-specific drug screen was performed on six drugs that interact with molecules downstream of progesterone, finding that the addition of progesterone to the model slightly changed the predicted effect of the drugs on the extracellular matrix.

Keywords

Heart disease; computational model; progesterone; estrogen; fibrosis

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