Elevated Glucose Impairs the Endothelial Cell Response to Shear Stress

Brower, Jeremy; Targovnik, Jerome; Bowen, Benjamin P.; Caplan, Michael R.; Massia, Stephen P.

doi:10.1007/s12195-009-0080-8

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…A previous study conducted on a cell culture model with high glucose concentration has reported a disturbed actin pattern when compared to control cells. 27 In our experiments the inflammatory effect of AGEs has also been established by the increased expression of sICAM in HUVECs (unpublished observations).…”

Section: Discussionsupporting

confidence: 64%

Interaction of glycated human serum albumin with endothelial cells in a hemodynamic environment: structural and functional correlates

2011

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Advanced glycation end products (AGEs) are known to be involved in the pathogenesis of several diseases, in particular diabetes, via signaling through their receptor. Numerous studies have been carried out on protein-sugar interactions at very high concentrations of the latter. The objective of this investigation was to determine the effects of nonenzymatic glycation induced by reducing sugars on the secondary structure of human serum albumin (HSA) under different physiological conditions and to correlate that with expression of RAGE (receptor for advanced glycation end products) on HUVECs (human umbilical vein endothelial cells) in a controlled hemodynamic environment. Our results indicate that RAGE expression is shear stress modulated and that glycated HSA enhances the expression further. The secondary structure of AGE-HSA derived from glucose at 20 mM contains higher α-helical content and elicits maximum expression of the receptor. The effect of shear stress at 10 dynes cm(-2) is independent of AGE-HSA.

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Section: Discussionsupporting

confidence: 64%

Interaction of glycated human serum albumin with endothelial cells in a hemodynamic environment: structural and functional correlates

2011

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“…Several recent papers suggest that elevated glucose inhibits endothelial cell elongation and alignment in response to shear stress due to changes in heparan sulfate proteoglycans in the glycocalyx [31]–[33]. We hypothesized that altered glucose levels may also disturb mechanotransduction via the adherens junction mechanosensor and its associated intracellular pathways.…”

Section: Introductionmentioning

confidence: 96%

Hypo- and Hyperglycemia Impair Endothelial Cell Actin Alignment and Nitric Oxide Synthase Activation in Response to Shear Stress

2013

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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/cm2 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.

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“…Furthermore, we study the alignment in response to altered glucose levels to simulate hypo- and hyperglycaemia or altered blood glucose levels associated with diabetes. As several studies report that altered glucose levels have an effect on endothelial cell alignment in response to fluid-induced shear stress 20 – 22 we wanted to understand if this would also affect the alignment of the brain microvascular endothelial cells when cultured on micropatterned lines.…”

Section: Introductionmentioning

confidence: 99%

Brain microvasculature endothelial cell orientation on micropatterned hydrogels is affected by glucose level variations

Hernández

Barbe

Pohlit

et al. 2021

Sci Rep

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This work reports on an effort to decipher the alignment of brain microvasculature endothelial cells to physical constrains generated via adhesion control on hydrogel surfaces and explore the corresponding responses upon glucose level variations emulating the hypo- and hyperglycaemic effects in diabetes. We prepared hydrogels of hyaluronic acid a natural biomaterial that does not naturally support endothelial cell adhesion, and specifically functionalised RGD peptides into lines using UV-mediated linkage. The width of the lines was varied from 10 to 100 µm. We evaluated cell alignment by measuring the nuclei, cell, and F-actin orientations, and the nuclei and cell eccentricity via immunofluorescent staining and image analysis. We found that the brain microvascular endothelial cells aligned and elongated to these physical constraints for all line widths. In addition, we also observed that varying the cell medium glucose levels affected the cell alignment along the patterns. We believe our results may provide a platform for further studies on the impact of altered glucose levels in cardiovascular disease.

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Elevated Glucose Impairs the Endothelial Cell Response to Shear Stress

Cited by 5 publications

References 58 publications

Interaction of glycated human serum albumin with endothelial cells in a hemodynamic environment: structural and functional correlates

Interaction of glycated human serum albumin with endothelial cells in a hemodynamic environment: structural and functional correlates

Hypo- and Hyperglycemia Impair Endothelial Cell Actin Alignment and Nitric Oxide Synthase Activation in Response to Shear Stress

Brain microvasculature endothelial cell orientation on micropatterned hydrogels is affected by glucose level variations

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