Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress.
Uncontrolled blood glucose in people with diabetes correlates with endothelial cell dysfunction, which contributes to accelerated atherosclerosis and subsequent myocardial infarction, stroke, and peripheral vascular disease. In vitro, both low and high glucose induce endothelial cell dysfunction; ho...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3680428?pdf=render |
| _version_ | 1819149490499616768 |
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| author | Steven Frank Kemeny Dannielle Solomon Figueroa Alisa Morss Clyne |
| author_facet | Steven Frank Kemeny Dannielle Solomon Figueroa Alisa Morss Clyne |
| author_sort | Steven Frank Kemeny |
| collection | DOAJ |
| description | Uncontrolled blood glucose in people with diabetes correlates with endothelial cell dysfunction, which contributes to accelerated atherosclerosis and subsequent myocardial infarction, stroke, and peripheral vascular disease. In vitro, both low and high glucose induce endothelial cell dysfunction; however the effect of altered glucose on endothelial cell fluid flow response has not been studied. This is critical to understanding diabetic cardiovascular disease, since endothelial cell cytoskeletal alignment and nitric oxide release in response to shear stress from flowing blood are atheroprotective. In this study, porcine aortic endothelial cells were cultured in 1, 5.55, and 33 mM D-glucose medium (low, normal, and high glucose) and exposed to 20 dynes/cm(2) shear stress for up to 24 hours in a parallel plate flow chamber. Actin alignment and endothelial nitric oxide synthase phosphorylation increased with shear stress for cells in normal glucose, but not cells in low and high glucose. Both low and high glucose elevated protein kinase C (PKC) levels; however PKC blockade only restored actin alignment in high glucose cells. Cells in low glucose instead released vascular endothelial growth factor (VEGF), which translocated β-catenin away from the cell membrane and disabled the mechanosensory complex. Blocking VEGF in low glucose restored cell actin alignment in response to shear stress. These data suggest that low and high glucose alter endothelial cell alignment and nitric oxide production in response to shear stress through different mechanisms. |
| first_indexed | 2024-12-22T14:02:26Z |
| format | Article |
| id | doaj.art-8def14d9ec9546a9889067e7801bfd72 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T14:02:26Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8def14d9ec9546a9889067e7801bfd722022-12-21T18:23:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6617610.1371/journal.pone.0066176Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress.Steven Frank KemenyDannielle Solomon FigueroaAlisa Morss ClyneUncontrolled blood glucose in people with diabetes correlates with endothelial cell dysfunction, which contributes to accelerated atherosclerosis and subsequent myocardial infarction, stroke, and peripheral vascular disease. In vitro, both low and high glucose induce endothelial cell dysfunction; however the effect of altered glucose on endothelial cell fluid flow response has not been studied. This is critical to understanding diabetic cardiovascular disease, since endothelial cell cytoskeletal alignment and nitric oxide release in response to shear stress from flowing blood are atheroprotective. In this study, porcine aortic endothelial cells were cultured in 1, 5.55, and 33 mM D-glucose medium (low, normal, and high glucose) and exposed to 20 dynes/cm(2) shear stress for up to 24 hours in a parallel plate flow chamber. Actin alignment and endothelial nitric oxide synthase phosphorylation increased with shear stress for cells in normal glucose, but not cells in low and high glucose. Both low and high glucose elevated protein kinase C (PKC) levels; however PKC blockade only restored actin alignment in high glucose cells. Cells in low glucose instead released vascular endothelial growth factor (VEGF), which translocated β-catenin away from the cell membrane and disabled the mechanosensory complex. Blocking VEGF in low glucose restored cell actin alignment in response to shear stress. These data suggest that low and high glucose alter endothelial cell alignment and nitric oxide production in response to shear stress through different mechanisms.http://europepmc.org/articles/PMC3680428?pdf=render |
| spellingShingle | Steven Frank Kemeny Dannielle Solomon Figueroa Alisa Morss Clyne Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. PLoS ONE |
| title | Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. |
| title_full | Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. |
| title_fullStr | Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. |
| title_full_unstemmed | Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. |
| title_short | Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. |
| title_sort | hypo and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress |
| url | http://europepmc.org/articles/PMC3680428?pdf=render |
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