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| Status |
Public on Nov 16, 2009 |
| Title |
Endothelial Responses to Atheroprone Flow |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In order to simulate the effects of shear stress in regions of the vasculature prone to developing atherosclerosis, we subjected human umbilical vein endothelial cells to reversing shear stress, in order to mimic hemodynamic conditions at the wall of the carotid sinus, a site of complex, reversing blood flow and commonly observed atherosclerosis. We compared the effects of reversing shear stress (time-average 1 dyne/cm2, maximum +11 dynes/cm2, minimum -11 dynes/cm2, 1 Hz), arterial steady shear stress (15 dynes/cm2), and low steady shear stress (1 dyne/cm2) in terms of gene expression, cell proliferation, and monocyte adhesiveness. Microarray analysis revealed most differentially expressed genes were similarly regulated by all three shear stress regimens when compared to static culture. Comparisons of the three shear stress regimens to each other allowed identification of 138 genes regulated by low average shear stress and 22 by fluid reversal. Functional assays indicated that low average shear stress induces increased cell proliferation as compared to high shear stress. Reversing shear stress was the only condition that induced monocyte adhesion. Monocyte adhesion was partially inhibited by incubation of the endothelial cells with ICAM-1 blocking antibody. Increased surface heparin sulfate proteoglycan expression was observed in cells exposed to reversing shear stress. When these cells were treated with heparinase III monocyte adhesion was significantly reduced. Our results suggest that low steady shear stress is the major impetus for differential gene expression and cell proliferation, while reversing flow regulates monocyte adhesion.
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| Overall design |
Gene expression in endothelial cells was measured after 24 hours of exposure to 15 dyne/cm2 steady shear stress, 1 dyne/cm2 steady shear stress, reversing flow, or static culture. Three independent experiments were performed using different lots of endothelial cells each time.
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| Contributor(s) |
Conway DE, Williams MR, Eskin SG, McIntire LV |
| Citation(s) |
19915176 |
| Submission date |
Jun 18, 2009 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Marcie R Williams |
| E-mail(s) |
marcie@gatech.edu
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| Organization name |
Georgia Institute of Technology
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| Department |
Biomedical Engineering
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| Lab |
Dr. Larry McIntire
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| Street address |
2300 Country Walk 3427
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| City |
Snellville |
| State/province |
GA |
| ZIP/Postal code |
30039 |
| Country |
USA |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (12)
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| GSM418608 |
Endothelial Cells, Low Shear Stress, 1 dyne/cm2, Replicate 1 |
| GSM418609 |
Endothelial Cells, High Shear Stress, 15 dyne/cm2, Replicate 1 |
| GSM418610 |
Endothelial Cells, Reversing Flow, Replicate 1 |
| GSM418611 |
Endothelial Cells, Static Culture, Replicate 1 |
| GSM418612 |
Endothelial Cells, Low Shear Stress, 1 dyne/cm2, Replicate 2 |
| GSM418613 |
Endothelial Cells, High Shear Stress, 15 dyne/cm2, Replicate 2 |
| GSM418614 |
Endothelial Cells, Reversing Flow, Replicate 2 |
| GSM418615 |
Endothelial Cells, Static Culture, Replicate 2 |
| GSM418616 |
Endothelial Cells, Low Shear Stress, 1 dyne/cm2, Replicate 3 |
| GSM418617 |
Endothelial Cells, High Shear Stress, 15 dyne/cm2, Replicate 3 |
| GSM418618 |
Endothelial Cells, Reversing Flow, Replicate 3 |
| GSM418619 |
Endothelial Cells, Static Culture, Replicate 3 |
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| Relations |
| BioProject |
PRJNA117357 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE16706_RAW.tar |
94.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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