scholarly journals High Glucose Reduces the Shear Stress-Induced CD59 Expression on EPCs through F-Actin Alteration

2019 ◽  
Vol 16 (s1) ◽  
pp. 87-87
Author(s):  
Na Liu ◽  
Xiaoyun Zhang ◽  
Yuzhen Ding ◽  
Hong Li ◽  
Xiumei Guan ◽  
...  
Keyword(s):  
Shear Stress ◽  
High Glucose ◽  
Cd59 Expression

High Glucose Alters Endothelial Cell Response to Shear Stress

2009 ◽  
Author(s):  
Steven F. Kemeny ◽  
Alisa Morss Clyne
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Cell Mechanics ◽  
High Glucose ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Focal Adhesions ◽  
Endothelial Cell Function

Endothelial cells line the walls of all blood vessels, where they maintain homeostasis through control of vascular tone, permeability, inflammation, and the growth and regression of blood vessels. Endothelial cells are mechanosensitive to fluid shear stress, elongating and aligning in the flow direction [1–2]. This shape change is driven by rearrangement of the actin cytoskeleton and focal adhesions [2]. Hyperglycemia, a hallmark of diabetes, affects endothelial cell function. High glucose has been shown to increase protein kinase C, formation of glucose-derived advanced glycation end-products, and glucose flux through the aldose reductase pathway within endothelial cells [3]. These changes are thought to be related to increased reactive oxygen species production [4]. While endothelial cell mechanics have been widely studied in healthy conditions, many disease states have yet to be explored. Biochemical alterations related to high glucose may alter endothelial cell mechanics.

Modulation of Rat Pial Arteriolar Responses to Flow by Glucose

2002 ◽  
Vol 97 (2) ◽  
pp. 471-477 ◽  
Author(s):  
Michael E. Ward ◽  
Lu Yan ◽  
Mark R. Angle
Keyword(s):  
Shear Stress ◽  
High Glucose ◽  
Glucose Concentration ◽  
Muscle Tone ◽  
Transmural Pressure ◽  
Intraluminal Pressure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pial Arterioles ◽  
Physiologic Saline

Background Pial arteriolar responses to flow contribute to regulation of cerebral perfusion and vary according to the transmural pressure to which the vessel is exposed. This study determined the effect of increased glucose concentration on the flow responses of pial arterioles at low and high levels of transmural pressure. Methods Pial arterioles from Sprague-Dawley rats were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by perfusion with air. Diameters were recorded at transmural pressures of 60 and 120 mmHg during superfusion with physiologic saline containing 5 mm D-glucose, 20 mm D-glucose, or 5 mm D-glucose and 15 mm L-glucose. Diameters during superfusion with saline containing 44 mm D-glucose were measured at an intraluminal pressure of 60 mmHg. Flow-diameter relationships (5-30 microl/min) were recorded during perfusion with the same solutions. Results Increasing D-glucose concentration caused constriction (P < 0.05) in endothelium-denuded but not in endothelium-intact arterioles. Addition of L-glucose caused constriction in endothelium-intact and -denuded vessels (P < 0.05 for both). At a D-glucose concentration of 5 mm and at low intraluminal pressure, flow elicits endothelium-dependent dilation such that shear stress remains constant. At a D-glucose concentration of 20 or 44 mm, after addition of L-glucose (15 mm), and at high intraluminal pressures, flow elicits constriction and shear stress is unregulated. Conclusions High glucose concentrations elicit increased basal arteriolar smooth muscle tone that is counteracted by release of endothelium-derived relaxing factors. Endothelium-dependent relaxation to flow (shear stress) is inhibited at high glucose concentrations.

scholarly journals High Glucose Activates YAP Signaling to Promote Vascular Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jeremy Ortillon ◽  
Jean-Christophe Le Bail ◽  
Elise Villard ◽  
Bertrand Léger ◽  
Bruno Poirier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
High Glucose ◽  
Oscillatory Flow ◽  
Vascular Inflammation ◽  
Vascular Complications ◽  
Diabetic Mice ◽  
Flow Conditions ◽  
Endothelial Inflammation

Background and AimsThe YAP/TAZ signaling is known to regulate endothelial activation and vascular inflammation in response to shear stress. Moreover, YAP/TAZ signaling plays a role in the progression of cancers and renal damage associated with diabetes. However, whether YAP/TAZ signaling is also implicated in diabetes-associated vascular complications is not known.MethodsThe effect of high glucose on YAP/TAZ signaling was firstly evaluated in vitro on endothelial cells cultured under static conditions or subjected to shear stress (either laminar or oscillatory flow). The impact of diabetes on YAP/TAZ signaling was additionally assessed in vivo in db/db mice.ResultsIn vitro, we found that YAP was dephosphorylated/activated by high glucose in endothelial cells, thus leading to increased endothelial inflammation and monocyte attachment. Moreover, YAP was further activated when high glucose was combined to laminar flow conditions. YAP was also activated by oscillatory flow conditions but, in contrast, high glucose did not exert any additional effect. Interestingly, inhibition of YAP reduced endothelial inflammation and monocyte attachment. Finally, we found that YAP is also activated in the vascular wall of diabetic mice, where inflammatory markers are also increased.ConclusionWith the current study we demonstrated that YAP signaling is activated by high glucose in endothelial cells in vitro and in the vasculature of diabetic mice, and we pinpointed YAP as a regulator of high glucose-mediated endothelial inflammation and monocyte attachment. YAP inhibition may represent a potential therapeutic opportunity to improve diabetes-associated vascular complications.

scholarly journals Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells

2008 ◽  
Vol 295 (5) ◽  
pp. H1966-H1973 ◽  
Author(s):  
Gyeong In Mun ◽  
Sang Mi An ◽  
Heonyong Park ◽  
Hanjoong Jo ◽  
Yong Chool Boo
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Arachidonic Acid ◽  
High Glucose ◽  
Critical Role ◽  
Antioxidant Effect ◽  
Laminar Shear Stress ◽  
Laminar Shear

Elevated blood glucose and free fatty acids induce oxidative stress associated with the incidence of cardiovascular disease. In contrast, laminar shear stress (LSS) plays a critical role in maintaining vascular health. The present study examined the mechanism for the antioxidant effect of LSS attenuating the oxidative stress induced by high glucose (HG) and arachidonic acid (AA) in human umbilical vein endothelial cells. HG and AA synergistically decreased cell viability and increased glutathione (GSH) oxidation and lipid peroxidation. The lipid peroxidation was markedly prevented by LSS as well as tetrahydrobiopterin (BH4) and GSH. LSS increased BH4 and GSH contents, and expression of GTP cyclohydrolase-1 and glutamylcysteine ligase (GCL) involved in their biosynthesis. Inhibition of GCL activity by DL-buthionine-(S,R)-sulfoximine and small-interfering RNA-mediated knockdown of GCL lessened the antioxidant effect of LSS. Therefore, it is suggested that LSS enhances antioxidant capacity of endothelial cells and thereby attenuates the oxidative stress caused by cardiovascular risk factors.

Abstract 169: Impaired Shear Stress-induced Endothelial Nitric Oxide Production in High Glucose Condition is Restored by Inhibiton via NADPH Consumption by Polyol Pathway Activation

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Tomio Umemoto ◽  
Masatoshi Kuroki ◽  
Hiroto Ueba ◽  
Masanobu Kawakami ◽  
Hideo Fujita ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Polyol Pathway ◽  
No Production ◽  
Pathway Activation ◽  
High Glucose Condition ◽  
Glucose Condition

Endothelial dysfunction leading to cardiovascular disease risk involves a decrease in nitric oxide (NO) production. In physiological conditions shear stress is a potent stimulation of endothelium-derived NO production and flow mediated NO production is regulated by the activation of endothelial NO synthase (eNOS). In endothelial cells, eNOS, aldose reductase (AR), a rate limiting enzyme of polyol pathway, and glutathione reductase (GR) share a NADPH as an obligate cofactor. In diabetec condition intracellular polyol pathway is activated and this may decrease shear stress-induced endothelial NO production and increase intracellular oxidative stress via inhibition of eNOS and GR by NADPH consumption. Therefore we investigated whethter AR inhibitor epalrestat improved endothelial NO production under high glucose condition to elucidate the mechanism of endothelial dysfunction in diabetes. We incubated human umbilical vein endothelial cells (HUVECs) in normal (5mM) and high (30mM) glucose condition for 72 hours, with or without epralrestat, or 100U/ml superoxide dismutase (SOD), respectively. After exchange of medium for Krebs’ buffer, HUVECs were exposed to 12dyne/cm2 steady laminar fluid shear stress for 5 minutes. NO release from HUVECs was measured as NO2 using a NOx analyzing HPLC system by Griess reaction. Next we harvested the cells in lysis buffer and analyzed phosphorylation of Akt (shear induced intracellular signal transduction) and eNOS by western blotting, and measured intracellular 8-OHdG and ratio of NADPH/NADP. In high glucose condition NO2 was decreased and 8-OHdG increased compared to low glucose. NO2 was restored and 8-OHdG was reduced by epalrestat significantly (p<0.01, p<0.05, respectively, vs. high glucose condition). In SOD-treated HUVECs, NO2 was not restored (n.s. vs. high glucose condition) despite of complete reduction of 8-OHdG (p<0.01). Both Akt and eNOS phosphorylation by shear stress was affected neither by high glucose, epalrestat nor SOD. Intracellular NADPH/NADP ratio was decreased in high glucose condition, but this reduction was restored by epalrestat. These results showed that polyol pathway activation plays a key role in endothelial NO production under high glucose condition via a cofactor NADPH.

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