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Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay
Published on: June 30, 2023
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Vascular endothelial cell morphology and alignment regulate VEGF-induced endothelial nitric oxide synthase activation
Aparna Bhattacharyya1, Kenneth A Barbee1
1School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.
Cytoskeleton (Hoboken, N.J.)
|May 22, 2024
Summary
Endothelial cell shape influences nitric oxide (NO) production. Aligned cells, under cytoskeletal tension, enhance VEGF-stimulated NO signaling, impacting vascular health and drug development.
Area of Science:
- Vascular biology and mechanotransduction.
- Endothelial cell (EC) biology and function.
- Biomedical engineering and biomaterials.
Background:
- Endothelial nitric oxide synthase (eNOS) dysfunction is linked to vascular diseases like atherosclerosis.
- Endothelial cell (EC) morphology and cytoskeletal organization influence eNOS regulation, especially under varying shear stress.
- The role of cytoskeletal prestress in ECs, particularly in the absence of shear, requires further investigation.
Purpose of the Study:
- To investigate the signaling pathways controlling VEGF-stimulated eNOS regulation in aligned ECs.
- To determine the impact of cytoskeletal tension on eNOS activation in elongated, aligned ECs.
- To elucidate the role of focal adhesion kinase (FAK) in VEGF-mediated eNOS signaling within the aligned EC phenotype.
Main Methods:
- Utilized anisotropic topographic cues to induce elongation and alignment in bovine aortic endothelial cells (BAECs).
- Administered Vascular Endothelial Growth Factor (VEGF) with and without cytoskeletal tension inhibitors (e.g., blebbistatin).
- Assessed phosphorylation levels of eNOS, AKT, and FAK using Western blotting.
Main Results:
- Phosphorylation of eNOS (ser1179), AKT (ser437), and FAK (Tyr397) was significantly higher in aligned ECs following VEGF stimulation.
- VEGF-induced signaling responses were abrogated by blebbistatin, indicating a critical role for cytoskeletal tension.
- Demonstrated the dependence of VEGF-mediated eNOS activation on FAK phosphorylation and the cytoskeletal machinery in aligned ECs.
Conclusions:
- Cytoskeletal tension in aligned ECs potentiates VEGF-stimulated eNOS activation through FAK and AKT signaling.
- This study highlights the importance of EC morphology and cytoskeletal mechanics in vascular signaling.
- Findings have implications for vascular graft design and drug development targeting vascular pathologies.
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