scholarly journals PPAR-αAgonist Fenofibrate Upregulates Tetrahydrobiopterin Level through Increasing the Expression of Guanosine 5′-Triphosphate Cyclohydrolase-I in Human Umbilical Vein Endothelial Cells

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jinbo Liu ◽  
Changlin Lu ◽  
Fuwang Li ◽  
Haining Wang ◽  
Liyun He ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide (NO) synthase. Guanosine 5′-triphosphate cyclohydrolase-I (GTPCH-I) is a key limiting enzyme for BH4 synthesis. In the present in vitro study, we investigated whether peroxisome proliferator-activated receptorα(PPAR-α) agonist fenofibrate could recouple eNOS by reversing low-expression of intracellular BH4 in endothelial cells and discussed the potential mechanisms. After human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) for 24 hours, the levels of cellular eNOS, BH4 and cell supernatant NO were significantly reduced compared to control group. And the fluorescence intensity of intracellular ROS was significantly increased. But pretreated with fenofibrate (10 umol/L) for 2 hours before cells were induced by LPS, the levels of eNOS, NO, and BH4 were significantly raised compared to LPS treatment alone. ROS production was markedly reduced in fenofibrate group than LPS group. In addition, our results showed that the level of intracellular GTPCH-I detected by western blot was increased in a concentration-dependent manner after being treated with fenofibrate. These results suggested that fenofibrate might help protect endothelial function and against atherosclerosis by increasing level of BH4 and decreasing production of ROS through upregulating the level of intracellular GTPCH-I.

scholarly journals Hydroxytyrosol Ameliorates Endothelial Function under Inflammatory Conditions by Preventing Mitochondrial Dysfunction

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Nadia Calabriso ◽  
Antonio Gnoni ◽  
Eleonora Stanca ◽  
Alessandro Cavallo ◽  
Fabrizio Damiano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mitochondrial Function ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflamed Endothelium

Mitochondria are fundamental organelles producing energy and reactive oxygen species (ROS); their impaired functions play a key role in endothelial dysfunction. Hydroxytyrosol (HT), a well-known olive oil antioxidant, exerts health benefits against vascular diseases by improving endothelial function. However, the HT role in mitochondrial oxidative stress in endothelial dysfunction is not clear yet. To investigate the HT effects on mitochondrial ROS production in the inflamed endothelium, we used an in vitro model of endothelial dysfunction represented by cultured endothelial cells, challenged with phorbol myristate acetate (PMA), an inflammatory, prooxidant, and proangiogenic agent. We found that the pretreatment of endothelial cells with HT (1–30 μmol/L) suppressed inflammatory angiogenesis, a crucial aspect of endothelial dysfunction. The HT inhibitory effect is related to reduced mitochondrial superoxide production and lipid peroxidation and to increased superoxide dismutase activity. HT, in a concentration-dependent manner, improved endothelial mitochondrial function by reverting the PMA-induced reduction of mitochondrial membrane potential, ATP synthesis, and ATP5β expression. In PMA-challenged endothelial cells, HT also promoted mitochondrial biogenesis through increased mitochondrial DNA content and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A. These results highlight that HT blunts endothelial dysfunction and pathological angiogenesis by ameliorating mitochondrial function, thus suggesting HT as a potential mitochondria-targeting antioxidant in the inflamed endothelium.

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.

Cell Shape Change and Cytosolic Ca2+ in Human Umbilical-Vein Endothelial Cells Stimulated with Thrombin

1992 ◽  
Vol 67 (03) ◽  
pp. 331-334 ◽  
Author(s):  
Haruhiko Sago ◽  
Kazuso linuma
Keyword(s):  
Endothelial Cells ◽  
Cell Size ◽  
Shape Change ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Calmodulin Antagonist ◽  
Human Umbilical Vein ◽  
Cell Shape Change ◽  
Umbilical Vein Endothelial Cells

SummaryWe quantified thrombin-induced endothelial cells shape change and investigated the role of Ca2+ in such shape change. We used the fluorescent Ca2+ indicator, fura2, to measure both shape change as cell size and intracellular free Ca2+ ([Ca2+]i), in cultured human umbilical-vein endothelial cells (HUVEC). Thrombin induced concentration-dependent decreases in cell size (percentage of cell size at 6 min after stimulation with 0.01 U/ml, 0.1 U/ml, or 1 U/ml thrombin) was 90.1 ± 1.5%, 78.1 ± 2.4%, and 40.9 ± 2.4%, respectively. Thrombin also increased [Ca2+]i in a concentration-dependent manner. Both depletion of extracellular Ca2+, and also the addition of W5, a calmodulin antagonist, inhibited thrombin-induced size reduction. These results indicate an association between shape change and [Ca2+]i mobilization in human endothelial cells stimulated by thrombin.

Relationship between erythropoietin and nitric oxide in the contraction of rat renal arcuate arteries and human umbilical vein endothelial cells

1999 ◽  
Vol 97 (4) ◽  
pp. 413-419 ◽  
Author(s):  
Xiao Chun WU ◽  
Edward J. JOHNS ◽  
Nicholas T. RICHARDS
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Human Erythropoietin ◽  
Low Concentrations ◽  
No Release ◽  
High Concentrations ◽  
Umbilical Vein Endothelial Cells

We have investigated the effects of recombinant human erythropoietin (EPO) on the responses of rat renal arcuate arteries to dopamine, noradrenaline and acetylcholine and on the release of NO from human umbilical vein endothelial cells (HUVEC) in culture. Noradrenaline induced a concentration-dependent constriction and acetylcholine a concentration-dependent relaxation of the vessels. The effects of dopamine were concentration-dependent, leading to relaxation of the vessels at low concentrations and contraction of the vessels at high concentrations. NG-Nitro-L-arginine methyl ester (L-NAME; 0.1 mM) did not change the vasoconstrictor responses to noradrenaline and dopamine, but inhibited the acetylcholine- and dopamine-induced vasorelaxation. Neither 0.1 nor 20 units·ml-1 EPO affected noradrenaline-induced constriction, or dopamine- or acetylcholine-induced relaxation, of the vessels. EPO at 20 units·ml-1 attenuated dopamine-induced constriction of the vessels. This effect was blunted by application of L-NAME, suggesting that EPO may stimulate dopamine-mediated NO release from these vessels. EPO stimulated NO release from the resting HUVEC in a concentration- and time-dependent manner, an effect that was inhibited by the presence of NG-nitro-L-arginine. These data suggest that, in vitro, EPO is able to stimulate NO release from rat renal arcuate arteries and HUVEC in culture. Whether these acute short-term actions can be related to the longer-term actions of EPO remains to be resolved.

scholarly journals Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Zhimin Zhang ◽  
Congying Wei ◽  
Yanfen Zhou ◽  
Tao Yan ◽  
Zhengqiang Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Human Umbilical Vein ◽  
Homologous Protein ◽  
Intracellular Ros ◽  
Underlying Mechanisms ◽  
Umbilical Vein Endothelial Cells

Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3. Prolonged Hcy treatment also upregulated glucose-regulated protein 78 (GRP78), activated protein kinase RNA-like ER kinase (PERK), and induced the expression of C/EBP homologous protein (CHOP) and the phosphorylation of NF-κb. The inhibition of NOX4 decreased the production of ROS and alleviated the Hcy-induced HUVEC apoptosis and ER stress. Blocking the PERK pathway partly alleviated Hcy-induced HUVEC apoptosis and the activation of NF-κb. Taken together, our results suggest that Hcy-induced mitochondrial dysfunction crucially modulated apoptosis and contributed to the activation of ER stress in HUVEC. The excessive activation of the PERK pathway partly contributed to Hcy-induced HUVEC apoptosis and the phosphorylation of NF-κb.

scholarly journals Effect of TNFα stimulation on expression of kidney risk inflammatory proteins in human umbilical vein endothelial cells cultured in hyperglycemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zaipul I. Md Dom ◽  
Caterina Pipino ◽  
Bozena Krolewski ◽  
Kristina O’Neil ◽  
Eiichiro Satake ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Systemic Exposure ◽  
In Vitro Study ◽  
Human Umbilical Vein ◽  
Intracellular Fraction ◽  
Inflammatory Proteins ◽  
Umbilical Vein Endothelial Cells ◽  
Extracellular Fraction

AbstractWe recently identified a kidney risk inflammatory signature (KRIS), comprising 6 TNF receptors (including TNFR1 and TNFR2) and 11 inflammatory proteins. Elevated levels of these proteins in circulation were strongly associated with risk of the development of end-stage kidney disease (ESKD) during 10-year follow-up. It has been hypothesized that elevated levels of these proteins in circulation might reflect (be markers of) systemic exposure to TNFα. In this in vitro study, we examined intracellular and extracellular levels of these proteins in human umbilical vein endothelial cells (HUVECs) exposed to TNFα in the presence of hyperglycemia. KRIS proteins as well as 1300 other proteins were measured using the SOMAscan proteomics platform. Four KRIS proteins (including TNFR1) were down-regulated and only 1 protein (IL18R1) was up-regulated in the extracellular fraction of TNFα-stimulated HUVECs. In the intracellular fraction, one KRIS protein was down-regulated (CCL14) and 1 protein was up-regulated (IL18R1). The levels of other KRIS proteins were not affected by exposure to TNFα. HUVECs exposed to a hyperglycemic and inflammatory environment also showed significant up-regulation of a distinct set of 53 proteins (mainly in extracellular fraction). In our previous study, circulating levels of these proteins were not associated with progression to ESKD in diabetes.

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