Abstract
Introduction
The goal of this study was to investigate how concurrent shear stress and tensile strain affect endothelial cell biomechanical responses.
Methods
Human coronary artery endothelial cells were exposed to concurrent pulsatile shear stress and cyclic tensile strain in a programmable shearing and stretching device. Three shear stress–tensile strain conditions were used: (1) pulsatile shear stress at 1 Pa and cyclic tensile strain at 7%, simulating normal stress/strain conditions in a healthy coronary artery; (2) shear stress at 3.7 Pa and tensile strain at 3%, simulating pathological stress/strain conditions near a stenosis; (3) shear stress at 0.7 Pa and tensile strain at 5%, simulating pathological stress/strain conditions in a recirculation zone. Cell morphology was quantified using immunofluorescence microscopy. Cell surface PECAM-1 phosphorylation, ICAM-1 expression, ERK1/2 and NF-κB activation were measured using ELISA or Western blot.
Results
Simultaneous stimulation from pulsatile shear stress and cyclic tensile strain induced a significant increase in cell area, compared to that induced by shear stress or tensile strain alone. The combined stimulation caused significant increases in PECAM-1 phosphorylation. The combined stimulation also significantly enhanced EC surface ICAM-1 expression (compared to that under shear stress alone) and transcriptional factor NF-κB activation (compared to that under control conditions).
Conclusion
Pulsatile shear stress and cyclic tensile strain could induce increased but not synergistic effect on endothelial cell morphology or activation. The combined mechanical stimulation can be relayed from cell membrane to nucleus. Therefore, to better understand how mechanical conditions affect endothelial cell mechanotransduction and cardiovascular disease development, both shear stress and tensile strain need to be considered.
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This study was in part supported by an American Heart Association Grant in Aid Award (16GRNT30440002).
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None for Daphne Meza, Bryan Musmacker, Elisabeth Steadman, Thomas Stransky, David A. Rubenstein, and Wei Yin.
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Meza, D., Musmacker, B., Steadman, E. et al. Endothelial Cell Biomechanical Responses are Dependent on Both Fluid Shear Stress and Tensile Strain. Cel. Mol. Bioeng. 12, 311–325 (2019). https://doi.org/10.1007/s12195-019-00585-0
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DOI: https://doi.org/10.1007/s12195-019-00585-0