Date of Award
James A. Stewart Jr.
Diabetes is one of the leading causes of death in the United States with around 30 million who suffer from diabetes and 84 million who are considered pre-diabetic. Diabetic individuals are at an increased risk for developing cardiovascular disease due to a stiffening of the left ventricle, which is thought to occur through fibroblast “activation” mediated by increased AGE/RAGE signaling. Advanced glycated end products (AGEs) accumulate within the body overtime and are accelerated under hyperglycemic conditions, and AGEs exert their effects by binding to their receptor (RAGE). Fibroblast “activation” is marked by elevated levels of α-smooth muscle actin expression and an increase in cell migration. While “active” fibroblast migration is increased during wound healing in a healthy individual, diabetics have decreased fibroblast migration to prolong wound healing. Therefore, the goal of this study was to determine how the AGE/RAGE signaling pathway impacts cell migration in non-diabetic and diabetic cardiac fibroblasts. Using isolated cardiac fibroblasts from non-diabetic and diabetic mice, migration was assessed with a migration assay. Diabetic fibroblasts have an increase in migration compared to non-diabetic fibroblasts whereas inhibiting the AGE/RAGE signaling pathway leads to a significant increase in fibroblast migration. The results suggest that the AGE/RAGE signaling cascade plays a role in cardiac fibroblast migration.
Harmon, Mallory B., "The Role of the Age/Rage Signaling Pathway in Cardiac Fibroblast Migration" (2019). Honors Theses. 1011.
Available for download on Friday, September 02, 2022