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Isolation and Profiling of Human Primary Mesenteric Arterial Endothelial Cells at the Transcriptome Level
Published on: March 14, 2022
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Proteomic and functional analysis on endothelial cell heterogeneity identifies key regulators in
Morgan Minjares1, Ruchi Jaiswal1, Hainan Li1
1Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, United States.
American Journal of Physiology. Cell Physiology
|November 11, 2025
Summary
Researchers found differences between aortic and dermal endothelial cells. Targeting WARS1 and SOD2 improved cell function and accelerated wound healing in diabetic mice, offering potential therapies for diabetes-related complications.
Area of Science:
- Vascular Biology
- Cellular Heterogeneity
- Proteomics
Background:
- Endothelial cells (ECs) are crucial for vascular homeostasis and neovascularization.
- EC functions differ based on location (macrovascular vs. microvascular) and metabolic conditions like hyperglycemia.
- Understanding EC heterogeneity is key to improving therapies and reducing side effects.
Purpose of the Study:
- To compare functional and proteomic differences between human aortic ECs (HAECs) and human dermal microvascular ECs (HDMVECs).
- To investigate the impact of high glucose on these EC types.
- To identify molecular targets for improving EC function, particularly in diabetic conditions.
Main Methods:
- Comparative analysis of HAECs and HDMVECs proliferation, migration, and permeability.
- Proteomic analysis to identify differentially expressed proteins.
- In vitro manipulation of WARS1 and SOD2 expression.
- In vivo study using a type 2 diabetic mouse wound model.
Main Results:
- HDMVECs showed faster proliferation but lower migration and permeability than HAECs.
- High glucose impaired migration and increased permeability in HDMVECs.
- Proteomic analysis identified 126 differentially abundant proteins, including WARS1 and SOD2.
- Reversing WARS1/SOD2 levels improved HDMVEC function; combined therapy normalized function under high glucose.
- Combination therapy accelerated wound closure and angiogenesis in diabetic mice.
Conclusions:
- Significant functional and proteomic differences exist between HAECs and HDMVECs.
- WARS1 and SOD2 are identified as key regulators of EC function under high glucose.
- Targeting WARS1 and SOD2 offers a promising therapeutic strategy for enhancing dermal angiogenesis and wound healing in diabetes.
