scholarly journals Protective Pleiotropic Effect of Flavonoids on NAD+Levels in Endothelial Cells Exposed to High Glucose

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Daniëlle M. P. H. J. Boesten ◽  
Saskia N. I. von Ungern-Sternberg ◽  
Gertjan J. M. den Hartog ◽  
Aalt Bast
Keyword(s):  
Endothelial Cells ◽  
Enzyme Activity ◽  
Aldose Reductase ◽  
High Glucose ◽  
Umbilical Vein ◽  
Polyol Pathway ◽  
Pleiotropic Effect ◽  
Protective Role ◽  
Parp Activation

NAD+is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD+levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quercetin, and flavone) during high glucose conditions in anin vitromodel using human umbilical vein endothelial cells (HUVECs). Additionally we assessed the ability of these flavonoids to inhibit aldose reductase enzyme activity. We have previously shown that flavonoids can inhibit PARP activation. Extending these studies, we here provide evidence that flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD+. In addition, we established that flavonoids are able to inhibit aldose reductase, the key enzyme in the polyol pathway. We conclude that this protective effect of flavonoids on NAD+levels is a combination of the flavonoids ability to inhibit both PARP activation and aldose reductase enzyme activity. This study shows that flavonoids, by a combination of effects, maintain the redox state of the cell during hyperglycemia. This mode of action enables flavonoids to ameliorate diabetic complications.

scholarly journals Ranirestat has a stronger inhibitory activity on aldose reductase and suppresses inflammatory reactions in high glucose–exposed endothelial cells

2016 ◽  
Vol 13 (4) ◽  
pp. 312-315 ◽  
Author(s):  
Yuji Ishibashi ◽  
Takanori Matsui ◽  
Takafumi Matsumoto ◽  
Hiroshi Kato ◽  
Sho-ichi Yamagishi
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Aldose Reductase ◽  
High Glucose ◽  
Inhibitory Activity ◽  
Umbilical Vein ◽  
Inflammatory Reactions ◽  
Human Umbilical Vein ◽  
Reductase Inhibitors ◽  
Umbilical Vein Endothelial Cells

Objective: Under diabetic conditions, glucose is converted to sorbitol via aldose reductase, whose process could contribute to diabetic vascular complications. However, effects of aldose reductase inhibitors are modest in diabetic patients. This may be attributed to weak inhibitory activity of aldose reductase inhibitors. We compared effects of ranirestat on endothelial cell damage with those of epalrestat. Materials and methods: Intracellular formations of sorbitol and superoxide were measured by liquid chromatography–mass spectrometry–mass spectrometry and dihydroethidium staining, respectively. Vascular cell adhesion molecule-1 gene expression was analysed by reverse transcription polymerase chain reaction. THP-1 cell adhesion to human umbilical vein endothelial cells was evaluated using a fluorescent probe. Results: High glucose significantly increased sorbitol levels, superoxide generation and vascular cell adhesion molecule-1 mRNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were prevented by 500 nM ranirestat, but not epalrestat except for superoxide production. Conclusion: Our present results suggest that ranirestat has a stronger inhibitory activity on aldose reductase than epalrestat and suppresses inflammatory reactions in high glucose–exposed human umbilical vein endothelial cells.

The Effects of Carnosine on High Glucose-Induced Apoptosis of Human Umbilical Vein Endothelial Cells

2011 ◽  
Vol 345 ◽  
pp. 365-369
Author(s):  
Yan Shi ◽  
Chun Jing Zhang
Keyword(s):  
Electron Microscopy ◽  
Flow Cytometry ◽  
Endothelial Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
Control Group ◽  
Human Umbilical Vein ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

.Purposes,To explore the effects of carnosine on high glucose-induced apoptosis of human umbilical vein endothelial cells (HUVECs). Methods HUVECs were cultured in vitro. The cellular apoptotic model was made by the addition of high glucose (25 mmol/L), the group of high glucose and carnosine was administered by the addition of high glucose (25 mmol/L) with carnosine (20 mmol/L). In addition, cell apoptosis was detected by the electron microscopy and AnnexinV/PI flow cytometry. Results Compared with the control group, high glucose could induce HUVECs apoptosis under electron microscopy and AnnexinV/PI flow cytometry, while 20 mmol/L carnosine could inhibit the apoptosis induced by high glucose significantly (##P <0.05). Conclusion In this study, carnosine could inhibit high-glucose induced apoptosis of human umbilical vein endothelial cells.

High Glucose, but Not Testosterone, Increases Platelet Aggregation Mediated by Endothelial Cells

2015 ◽  
Vol 4 (3) ◽  
pp. 205
Author(s):  
Ikhlas Muhammad Jenie ◽  
Budi Mulyono ◽  
Soedjono Aswin ◽  
Sri Kadarsih Soejono
Keyword(s):  
Endothelial Cells ◽  
Platelet Aggregation ◽  
High Glucose ◽  
Platelet Rich Plasma ◽  
Umbilical Vein ◽  
In Vitro Study ◽  
Traditional Risk Factor ◽  
Main Effect ◽  
Effect Of Glucose

Endothelial cells inhibit platelet aggregation by releasing thromboregulators, such as prostacyclin and nitric oxide. Male subject is a traditional risk factor for cardiovascular diseases. Platelet hyperreactivity has been frequently found in patient with diabetes mellitus. To examine whether testosterone and high glucose modify platelet aggregation through endothelial cells, we did an in vitro study using endothelial cells culture from human umbilical vein (HUVEC). Treatments were performed in HUVEC sub culture as either normoglucose (5.6 mM) or high glucose (22.4 mM) medium, with or without testosterone (0, 1, 10, 100 nM), for 24 hours. HUVEC were trypsinized, resuspended, and then incubated with platelet rich plasma from healthy male donors with ratio 1:10<sup>4</sup> for 3 minutes. Platelet aggregation measured by turbidimetry methode. This study showed that testosterone did not significantly influence platelet aggregation through endothelial cells in normoglucose (<em>p </em>= 0.144) or high glucose (<em>p </em>= 0.916) medium. There was no main effect of testosterone (<em>p </em>= 0.73) as well as no interaction between testosterone and glucose (<em>p </em>= 0.69), but there was a main effect of glucose (<em>p </em>= 0.004), to platelet aggregation through endothelial cells. In conclusion, high glucose, but not testosterone, inhibits platelet aggregation mediated by endothelial cells.

scholarly journals Protective Role of Antioxidant Huskless Barley Extracts on TNF-α-Induced Endothelial Dysfunction in Human Vascular Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Zhanghua Liao ◽  
Haoran Cai ◽  
Zekun Xu ◽  
Jing Wang ◽  
Chen Qiu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Cell Model ◽  
Umbilical Vein ◽  
Antioxidant Properties ◽  
Protective Role ◽  
Antioxidant Power ◽  
Barley Cultivars ◽  
Umbilical Vein Endothelial Cells

Oxidative stress and inflammation are considered as two key factors that contribute to the development of atherosclerosis. This study was to investigate the antioxidant capacity of huskless barley and to explore its protective functions through the regulation of the antioxidant defense and inflammatory response in human umbilical vein endothelial cells (HUVEC). The oxygen radical absorbance capacity (ORAC), ferric-reducing antioxidant power (FRAP), and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) scavenging capacity of water and alkali extracts of the polysaccharides from nine huskless barley varieties were investigatedin vitro. The antioxidant properties of the alkaline extracts were more pronounced than those of the water extracts. The results from the cell model showed that pretreatment of HUVEC with the water or alkaline extracts of the polysaccharides from the huskless barley cultivars QHH and NLGL decreased the levels of reactive oxygen species (ROS), monocyte chemotactic protein 1 (MCP-1), and vascular cell adhesion molecule 1 (VCAM-1) but increased the level of superoxide dismutase (SOD) and maintained cell viability. Huskless barley polysaccharide extracts exhibited the vasodilatory effect of inhibiting angiotensin-converting enzyme (ACE) production. These discoveries revealed the potent protective functions of barley in oxidative damage and a potential role for barley in preventing chronic inflammation in cardiovascular diseases.

scholarly journals High Glucose, but Not Testosterone, Increases Platelet Aggregation Mediated by Endothelial Cells

2015 ◽  
Vol 4 (3) ◽  
pp. 205
Author(s):  
Ikhlas Muhammad Jenie ◽  
Budi Mulyono ◽  
Soedjono Aswin ◽  
Sri Kadarsih Soejono
Keyword(s):  
Endothelial Cells ◽  
Platelet Aggregation ◽  
High Glucose ◽  
Platelet Rich Plasma ◽  
Umbilical Vein ◽  
In Vitro Study ◽  
Traditional Risk Factor ◽  
Main Effect ◽  
Effect Of Glucose

Endothelial cells inhibit platelet aggregation by releasing thromboregulators, such as prostacyclin and nitric oxide. Male subject is a traditional risk factor for cardiovascular diseases. Platelet hyperreactivity has been frequently found in patient with diabetes mellitus. To examine whether testosterone and high glucose modify platelet aggregation through endothelial cells, we did an in vitro study using endothelial cells culture from human umbilical vein (HUVEC). Treatments were performed in HUVEC sub culture as either normoglucose (5.6 mM) or high glucose (22.4 mM) medium, with or without testosterone (0, 1, 10, 100 nM), for 24 hours. HUVEC were trypsinized, resuspended, and then incubated with platelet rich plasma from healthy male donors with ratio 1:10<sup>4</sup> for 3 minutes. Platelet aggregation measured by turbidimetry methode. This study showed that testosterone did not significantly influence platelet aggregation through endothelial cells in normoglucose (<em>p </em>= 0.144) or high glucose (<em>p </em>= 0.916) medium. There was no main effect of testosterone (<em>p </em>= 0.73) as well as no interaction between testosterone and glucose (<em>p </em>= 0.69), but there was a main effect of glucose (<em>p </em>= 0.004), to platelet aggregation through endothelial cells. In conclusion, high glucose, but not testosterone, inhibits platelet aggregation mediated by endothelial cells.

scholarly journals Atorvastatin reduces the expression of aldo-keto reductases in HUVEC and PTEC. A new approach to influence the polyol pathway

2009 ◽  
Vol 32 (3) ◽  
pp. 219 ◽  
Author(s):  
Tobias F Ruf ◽  
Susanne Quintes ◽  
Paula Sternik ◽  
Uwe Gottmann
Keyword(s):  
Small Intestine ◽  
Aldose Reductase ◽  
Umbilical Vein ◽  
Mevalonic Acid ◽  
Polyol Pathway ◽  
Pleiotropic Effect ◽  
Aldehyde Reductase ◽  
Control Medium ◽  
Key Enzyme ◽  
Proximal Tubular Epithelial Cells

Purpose: Increased flux of glucose via the polyol pathway, oxidative stress and ischaemia lead to the upregulation of the aldose reductase (AR), the key enzyme of the polyol pathway. This adversely affects the organism and can in part be reduced by inhibition of the enzyme. Methods: In this study, we examined the effect of the HMG-CoA-reductase inhibitor atorvastatin on the expression of aldose reductase (AR, AKR1B1), aldehyde reductase (AldR, AKR1A1) and small intestine reductase (SIR, AKR1B10) in human umbilical vein endothelial cells (HUVEC) and human proximal tubular epithelial cells (PTEC) by RT-PCR. Results: In HUVEC, atorvastatin reduces the expression of aldehyde reductase and aldose reductase compared with control medium (-20% and -12% respectively, P < 0.05), while small intestine reductase is not expressed. In PTEC no regulation of aldehyde reductase and aldose reductase by atorvastatin could be measured, while the expression of small intestine reductase was reduced by 37% compared with control medium (P < 0.05). The reduction observed was not abolished by the addition of mevalonic acid. Conclusion: The reduction of members of the aldo-keto-reductase family by atorvastatin is a novel way to influence the polyol pathway and a new pleiotropic effect of atorvastatin.

scholarly journals The CREB/KMT5A complex regulates PTP1B to modulate high glucose-induced endothelial inflammatory factor levels in diabetic nephropathy

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Ting Huang ◽  
Xue Li ◽  
Fei Wang ◽  
Lihong Lu ◽  
Wenting Hou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Promoter Activity ◽  
Umbilical Vein ◽  
Tyrosine Phosphatase ◽  
Inflammatory Factors ◽  
Inflammatory Factor

AbstractDiabetic nephropathy (DN) is the primary microvascular complication of diabetes mellitus and may result in end-stage renal disease. The overproduction of various inflammatory factors is involved in the pathogenesis of DN. Protein tyrosine phosphatase 1B (PTP1B) modulates the expression of a series of cytokines and nuclear factor kappa B (NF-κB) activity. cAMP response element-binding protein (CREB) and lysine methyltransferase 5A (KMT5A) have been reported to participate in the maintenance of a healthy endothelium. In the present study, we hypothesise that CREB associates with KMT5A to modulate PTP1B expression, thus contributing to high glucose-mediated glomerular endothelial inflammation. Our analyses revealed that plasma inflammatory factor levels, glomerular endothelial p65 phosphorylation and PTP1B expression were increased in DN patients and rats. In vitro, high glucose increased endothelial inflammatory factor levels and p65 phosphorylation by augmenting PTP1B expression in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose decreased CREB and KMT5A expression. CREB overexpression and KMT5A overexpression both inhibited high glucose-induced PTP1B expression, p65 phosphorylation and endothelial inflammatory factor levels. si-CREB- and sh-KMT5A-induced p65 phosphorylation and endothelial inflammatory factor levels were reversed by si-PTP1B. Furthermore, CREB was associated with KMT5A. Mechanistic research indicated that CREB and histone H4 lysine 20 methylation (H4K20me1, a downstream target of KMT5A) occupy the PTP1B promoter region. sh-KMT5A augmented PTP1B promoter activity and activated the positive effect of si-CREB on PTP1B promoter activity. Our in vivo study demonstrated that CREB and KMT5A were downregulated in glomerular endothelial cells of DN patients and rats. In conclusion, CREB associates with KMT5A to promote PTP1B expression in vascular endothelial cells, thus contributing to hyperglycemia-induced inflammatory factor levels in DN patients and rats.

Perturbation of Platelet Adhesion to Endothelial Cells by Plasminogen Activation In Vitro

1997 ◽  
Vol 78 (02) ◽  
pp. 934-938 ◽  
Author(s):  
Hsiun-ing Chen ◽  
Yueh-I Wu ◽  
Yu-Lun Hsieh ◽  
Guey-Yueh Shi ◽  
Meei-Jyh Jiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Platelet Adhesion ◽  
Treatment Time ◽  
Shape Change ◽  
Umbilical Vein ◽  
Tissue Type ◽  
Apical Surface ◽  
Plasminogen Activation

SummaryTo investigate whether the endothelium-platelet interactions may be altered by plasminogen activation, cultured human umbilical vein endothelial cells (ECs) were treated with tissue-type plasminogen activator (t-PA) in the presence of plasminogen, and platelet adhesion to ECs was subsequently measured by using a tapered flow chamber. Our results demonstrated that platelets adhered more readily to t-PA treated EC monolayer than to the control monolayer at all shear stress levels tested. This phenomenon was treatment time-dependent and dose-dependent, and it could be blocked by adding plasmin inhibitors, such as e-amino caproic acid and aprotinin. Adherent platelets on t-PA treated EC monolayer underwent more severe shape change than those on the control monolayer. While the extracellular matrix directly treated with t-PA attracted less platelets than the control matrix did, platelet adhesion to the matrix that was produced by t-PA-treated ECs was unaltered. These data suggest that t-PA treatment on ECs compromised antiplatelet-adhesion capability on their apical surface without altering the reactivity of their extracellular matrix towards platelets.

Desmopressin (DDAVP) Enhances Platelet Adhesion to the Extracellular Matrix of Cultured Human Endothelial Cells through Increased Expression of Tissue Factor

1997 ◽  
Vol 77 (05) ◽  
pp. 0975-0980 ◽  
Author(s):  
Angel Gálvez ◽  
Goretti Gómez-Ortiz ◽  
Maribel Díaz-Ricart ◽  
Ginés Escolar ◽  
Rogelio González-Sarmiento ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Procoagulant Activity ◽  
Experimental Conditions ◽  
Chromogenic Assay

SummaryThe effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DD A VP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin®, 20 U/ml). Perfusions were run for 5 min at a shear rate of 800 s1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p <0.05 and p <0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p <0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

Sign in / Sign up

Export Citation Format

Share Document