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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Pharmaceutical Sciences
First Advisor
Jiemei Wang
Abstract
Endothelial cells (ECs) play a critical role in managing vascular homeostasis and neovascularization. EC functions vary significantly depending on their anatomic locations, especially for ECs forming macrovascular versus microvascular vessels. ECs possess heterogenic signaling pathways, energy metabolism, and cellular behaviors to handle physiologic and hyperglycemic conditions. These variations can impact the efficacy of pharmacotherapy and influence the likelihood of unexpected side effects. In this study, we compared human aortic ECs (HAECs) and human dermal microvascular ECs (HDMVECs) to observe the functional and proteomic differences potentially contributing to EC heterogeneity. Compared to HAECs, HDMVECs exhibited faster proliferation, but lower migration and permeability. Under high glucose conditions, migration function worsened for both cell types whereas proliferation was unaffected and permeability increased for HDMVECs. Using proteomic analysis, we identified 126 proteins whose abundance was significantly different between HAECs and HDMVECs. DAVID analysis of these proteins revealed their biological processes, cellular compartments, molecular functions and pathways. Furthermore, under high glucose conditions, WARS1 was increased while SOD2 was decreased. Reversing WARS1 or SOD2 expression levels improved HDMVEC migration and permeability functions. Our studies provide novel molecular insights into EC heterogeneity and identified WARS1 and SOD2 as potential targets for dermal angiogenesis during tissue repair.
Recommended Citation
Minjares, Morgan, "The Impact Of Heterogeneity On Endothelial Function Under Hyperglycemia" (2025). Wayne State University Dissertations. 4261.
https://digitalcommons.wayne.edu/oa_dissertations/4261