scholarly journals Porphyromonas gingivalis Induces Apoptosis and Autophagy via ER Stress in Human Umbilical Vein Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Masaaki Hirasawa ◽  
Tomoko Kurita-Ochiai
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Dna Fragmentation ◽  
Porphyromonas Gingivalis ◽  
Umbilical Vein ◽  
Annexin V ◽  
Human Umbilical Vein ◽  
Increased Risk ◽  
Umbilical Vein Endothelial Cells

It has been reported that periodontitis is associated with an increased risk of atherosclerosis. Accumulating evidence suggests that endothelial dysfunction is an early marker for atherosclerosis. To determine how periodontal infections contribute to endothelial dysfunction, we examined the effect of Porphyromonas gingivalis on human umbilical vein endothelial cells (HUVEC). P. gingivalis significantly suppressed the viability of HUVEC, induced DNA fragmentation and annexin V staining, and increased caspase-3, caspase-8, and caspase-9 activities. P. gingivalis also increased the expression of GADD153 and GRP78 and caspase-12 activity. Further, P. gingivalis induced autophagy, as evidenced by increased LC3-II and Beclin-1 levels. The suppression of P. gingivalis-induced autophagy by silencing of LC3 with siRNA significantly increased P. gingivalis-induced apoptosis. ER stress inhibitor, salubrinal, suppressed apoptosis and autophagy by inhibiting P. gingivalis-induced DNA fragmentation and LC3-II expression. These data suggest that P. gingivalis infection induces ER stress-mediated apoptosis followed by autophagic response that protects HUVEC from P. gingivalis-mediated apoptosis, potentially amplifying proatherogenic mechanisms in the perturbed vasculature.

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 Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Martha Lappas
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Histone Deacetylase ◽  
Proinflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Vascular Diseases ◽  
Transcriptional Level ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB (NF-κB). The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known. The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8), COX-prostaglandin system, ECM remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to leukocytes. Loss of SIRT6 increased the expression of NF-κB, whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity. Taken together, these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential pharmacological target for inflammatory vascular diseases.

Tetrahydrobiopterin correctsEscherichia coliendotoxin-induced endothelial dysfunction

2005 ◽  
Vol 289 (4) ◽  
pp. H1752-H1757 ◽  
Author(s):  
Friedrich Mittermayer ◽  
Johannes Pleiner ◽  
Georg Schaller ◽  
Stefan Zorn ◽  
Khodadad Namiranian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Acute Inflammation ◽  
Umbilical Vein ◽  
Oxidant Stress ◽  
Double Blind ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Acute inflammation causes endothelial dysfunction, which is partly mediated by oxidant stress and inactivation of nitric oxide. The contribution of depletion of tetrahydrobiopterin (BH4), the cofactor required for nitric oxide generation, is unclear. In this randomized, double-blind, three-way crossover study, forearm blood flow (FBF) responses to ACh and glyceryltrinitrate (GTN) were measured before and 3.5 h after infusion of Escherichia coli endotoxin (LPS, 20 IU/kg iv) in eight healthy men. The effect of intra-arterial BH4(500 μg/min), placebo, or vitamin C (24 mg/min) was studied on separate days 3.5 h after LPS infusion. In addition, human umbilical vein endothelial cells were incubated for 24 h with vitamin C and LPS. ACh and GTN caused dose-dependent forearm vasodilation. The FBF response to ACh, which was decreased by 23 ± 17% ( P < 0.05) by LPS infusion, was restored to baseline reactivity by BH4and vitamin C. FBF responses to GTN were not affected by BH4or vitamin C. LPS increased leukocyte count, high-sensitivity C-reactive protein, IL-6, IL-1β, IFN-γ, monocyte chemoattractant protein-1, pulse rate, and body temperature and decreased platelet count and vitamin C concentration. Vitamin C increased forearm plasma concentration of BH4by 32% ( P < 0.02). Incubation with LPS and vitamin C, but not LPS alone, increased intracellular BH4concentration in human umbilical vein endothelial cells. Impaired endothelial function during acute inflammation can be restored by BH4or vitamin C. Vitamin C may exert some of its salutary effects by increasing BH4concentration.

Low nanomolar caffeic acid attenuates high glucose-induced endothelial dysfunction in primary human umbilical-vein endothelial cells by affecting NF-κB and Nrf2 pathways

BioFactors ◽  
2016 ◽  
Vol 43 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Deborah Fratantonio ◽  
Antonio Speciale ◽  
Raffaella Canali ◽  
Lucia Natarelli ◽  
Daniela Ferrari ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Caffeic Acid ◽  
High Glucose ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

scholarly journals CTRP3 Protects against High Glucose-Induced Cell Injury in Human Umbilical Vein Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Fang Wang ◽  
Linlin Zhao ◽  
Yingguang Shan ◽  
Ran Li ◽  
Guijun Qin
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Cell Injury ◽  
Umbilical Vein ◽  
Cell Loss ◽  
Inflammatory Factors ◽  
Therapeutic Drug ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Aims. Inflammation was closely associated with diabetes-related endothelial dysfunction. C1q/tumor necrosis factor-related protein 3 (CTRP3) is a member of the CTRP family and can provide cardioprotection in many cardiovascular diseases via suppressing the production of inflammatory factors. However, the role of CTRP3 in high glucose- (HG-) related endothelial dysfunction remains unclear. This study evaluates the effects of CTRP3 on HG-induced cell inflammation and apoptosis. Materials and Methods. To prevent high glucose-induced cell injury, human umbilical vein endothelial cells (HUVECs) were pretreated with recombinant CTRP3 for 1 hour followed by normal glucose (5.5 mmol/l) or high glucose (33 mmol/l) treatment. After that, cell apoptosis and inflammatory factors were determined. Results. Our results demonstrated that CTRP3 mRNA and protein expression were significantly decreased after HG exposure in HUVECs. Recombinant human CTRP3 inhibited HG-induced accumulation of inflammatory factors and cell loss in HUVECs. CTRP3 treatment also increased the phosphorylation levels of protein kinase B (AKT/PKB) and the mammalian target of rapamycin (mTOR) in HUVECs. CTRP3 lost its inhibitory effects on HG-induced cell inflammation and apoptosis after AKT inhibition. Knockdown of endogenous CTRP3 in HUVECs resulted in increased inflammation and decreased cell viability in vitro. Conclusions. Taken together, these findings indicated that CTRP3 treatment blocked the accumulation of inflammatory factors and cell loss in HUVECs after HG exposure through the activation of AKT-mTOR signaling pathway. Thus, CTRP3 may be a potential therapeutic drug for the prevention of diabetes-related endothelial dysfunction.

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