Umbilical Vein Endothelial Cell Dysfunction Research Articles

LncRNA FENDRR Servers as a Possible Marker of Essential Hypertension and Regulates Human Umbilical Vein Endothelial Cells Dysfunction via miR-423-5p/Nox4 Axis.

PurposeEssential hypertension (EH) is an intricate non-communicable infirmity and lncRNAs are validated as essential mediators in EH. The study aimed to propose the expression pattern of FENDRR and miR-423-5p, substantiate the potential mechanism of FENDRR/miR-423-5p/Nox4 axis in EH.Patients and MethodsThe expression of FENDRR and miR-423-5p was evaluated by qRT-PCR and the clinical significance was explored by the ROC curve. Pearson correlation indicated the relationship between FENDRR and miR-423-5p. The function of FENDRR and miR-423-5p on HUVECs was clarified by CCK-8 assay, Transwell assay, and flow cytometry. Western blot was used to assess the relative protein expression of Nox4.ResultsFENDRR was highly expressed and miR-423-5p was lowly expressed in EH patients and a negative correlation between them was determined. FENDRR might serve as a predictive diagnosis in differentiating EH patients. Knockdown of FENDRR or overexpression of miR-423-5p showed expansionary effects in cell proliferation, cell migration, and inhibiting cell apoptosis. Meanwhile, miR-423-5p was determined as a target of FENDRR and mediated the function of FENDRR on HUVECs. Moreover, Nox4 is a down-streaming target gene of miR-423-5p. The protein expression of Nox4 was regulated by the alternation of miR-423-5p expression.ConclusionFENDRR played an energetic role in EH and contributed to HUVECs dysfunction by restricting cell proliferation, suppressing cell migration, and accelerating cell apoptosis by manipulating the miR-423-5p/Nox4 axis.

MiR-320/VEGFA axis affects high glucose-induced metabolic memory during human umbilical vein endothelial cell dysfunction in diabetes pathology

The “metabolic memory”, a phenomenon that the target cell remembers the early hyperglycemia, has been reported to be a critical issue in diabetes pathogenesis. Here, we confirmed the inducible effects of high glucose (HG) and HG followed by normal glucose (HN) upon the proliferation and the tube formation capacity of human umbilical vein endothelial cells (HUVECs), as well as the suppressive effects of HG and HN on HUVEC apoptosis. In the meantime, the miR-320 expression could be dramatically downregulated (** and ## P < 0.01), whereas VEGFA expression (** and ## P < 0.01) and VEGFA, PKC, and RAGE protein levels could be remarkably induced via HG and HN stimulation. More importantly, the effects of HG and HN were not significantly different, suggesting the existence of high glucose-induced metabolic memory and the involvement of miR-320 and VEGFA in high glucose-induced metabolic memory in HUVECs. Consistently, miR-320 overexpression significantly reversed the effects of HG and HN on HUVECs (* and # P < 0.05, ** and ## P < 0.01). miR-320 suppressed the expression of VEGFA via direct binding to the 3′-UTR of VEGFA mRNA, therefore suppressing high glucose-induced metabolic memory (** P < 0.01); the effects of miR-320 overexpression on HUVECs could be reversed by VEGFA overexpression (# P < 0.05, ## P < 0.01), indicating that miR-320/VEGFA axis modulates the proliferation, apoptosis, and the angiogenesis capacity of HUVECs. In conclusion, we demonstrate that miR-320/VEGFA axis is crucial to high glucose-induced metabolic memory during HUVEC dysfunction and may be involved in the pathology of diabetes.

Plantamajoside from Plantago asiatica modulates human umbilical vein endothelial cell dysfunction by glyceraldehyde-induced AGEs via MAPK/NF-\u03baB

BackgroundPlantago asiatica has been traditionally used for traditional medicine around East Asia. Plantamajoside (PM), which is isolated from this plant, is known for biological properties including anti-inflammation and antioxidant activity. To demonstrate the biological activity of PM against endothelial dysfunction induced by advanced glycation end-products (AGEs), a cellular inflammatory mechanism system was evaluated in human umbilical vein endothelial cells (HUVECs).MethodsWe obtained PM through previous research in our laboratory. We formed the AGEs from bovine serum albumin with glyceraldehyde in the dark for seven days. To confirm the modulation of the inflammatory mechanism in endothelial dysfunction, we quantified the various pro-inflammatory cytokines and endothelial dysfunction-related proteins in the HUVECs with Western blotting and with real-time and quantitative real-time polymerase chain reactions.ResultsCo-treatment with PM and AGEs significantly suppressed inflammatory cytokines and adhesion molecule expression. Moreover, the PM treatment for down-regulated inflammatory signals and blocked monocyte adhesion on the HUVECs.ConclusionsTheses results demonstrated that PM, as a potential natural compound, protects AGE-induced endothelial cells against inflammatory cellular dysfunction.

Protective Effect of Irisin on Atherosclerosis via Suppressing Oxidized Low Density Lipoprotein Induced Vascular Inflammation and Endothelial Dysfunction.

Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.

Role of SIRT3 in Angiotensin II-induced human umbilical vein endothelial cells dysfunction.

BackgroundSIRT3, a member of the sirtuin family of NAD+-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions. Previous researches show an important role of SIRT3 in regulating the production of reactive oxygen species (ROS), and highlight the ability of SIRT3 to protect cells from oxidative damage. A key substance of renin-angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells dysfunction by increasing the production of ROS. In this paper, we focus on the role of SIRT3 in AngII-induced human umbilical vein endothelial cells (HUVECs) dysfunction.MethodsTo study the influence of AngII on SIRT3 expression, HUVECs were treated with AngII of 10−7, 10−6, 10−5 mol/L for 24 h. SIRT3 expression was detected by wester-blotting analysis and RT-PCR. In addition, to research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS generation of each group were detected.ResultsHere we show that AngII treatment could increase generation of ROS, and decrease eNOS activity and total level of NO, while upregulated eNOS expression as a compensatory mechanism. The stimulation of AngII upregulated the expression of SIRT3 in HUVECs. SIRT3 siRNA worsen the AngII-induced effects above, besides, downregulated eNOS protein expression.ConclusionThese data suggest that SIRT3 plays a role of protection in AngII-induced HUVECs dysfunction via regulation of ROS generation.

Preventative Effects of 4,4'‐Diphenylmethane‐bis(methyl) Carbamate Isolated from Cortex Mori on Human Umbilical Vein Endothelial Cell Dysfunction Induced by Advanced Glycation End Products

Advanced glycation end-products (AGEs) have been regarded as an initial motivating factor in the pathogenesis of endothelial dysfunction in diabetic complications. 4,4'-Diphenylmethane-bis(methyl) carbamate (DMPC), a carbamate compound, was isolated from Cortex Mori and its prevention effects against AGEs-induced endothelial dysfunction were studied. 4,4'-Diphenylmethane-bis(methyl) carbamate significantly reduced cell apoptosis to normal level at 10⁻⁹ mol/L concentration. Advanced glycation end-products up-regulated the expression of Bad and Bax and down-regulated Bcl-2 proteins, and pretreatment with DMPC significantly down-regulated Bad and Bax while up-regulating Bcl-2 expressions. In addition, ICAM (intercellular adhesion molecule)-1 and TGF (transforming growth factor)-β1 expressions in human umbilical vein endothelial cell (HUVEC) were significantly enhanced by AGEs. More importantly, these increases of ICAM-1 and TGF-β1 expressions were reduced meaningfully with the pretreatment of DMPC. All the results showed DMPC had prevention effects against the progression of AGE-induced endothelial dysfunction, and this compound might be a promising agent against endothelial dysfunction in diabetic vascular complications.

Endothelial dysfunction and vascular inflammation in Type 2 diabetes: interaction of AGE/RAGE and TNF-α signaling

the receptor for advanced glycation end products (RAGE) interacts with a diverse range of endogenous ligands termed advanced glycation end products (AGEs), which are formed by the Maillard reaction, a nonenzymatic process linking reducing sugar groups to proteins, lipids, and nucleic acids. AGEs

Study on the action of resistin-induced human umbilical vein endothelial cell dysfunction

The aim of this paper was to investigate the effects of resistin on human umbilical vein endothelial cells (HUVECs), and to explore its role and mechanism of action in atherosclerosis. HUVECs were incubated with recombinant human resistin (0, 50, 100 ng/mL) for 24 h. ICAM-1, VCAM-1 and reactive oxygen species (ROS) were assayed by flow cytometer. ET-1, eNOS and iNOS mRNA expression were measured by semi-quantitative RT-PCR. Incubation of HUVECs with resistin resulted in an increase in ICAM-1 expression and ET-1 mRNA expression. However, resistin had no effect on VCAM-1 expression and ROS release. eNOS and iNOS mRNA expression were not altered by resistin stimulation. Adipokine resistin exerted a direct effect in promoting HUVEC dysfunction by promoting ICAM-1 and ET-1 expression. These data suggest that adipocyte-endothelium cross-talk might play an important role in the pathogenesis of cardiovascular disease in diabetes mellitus.

Gestational diabetes and the adenosine/ l-Arginine/nitric oxide (ALANO) pathway in human umbilical vein endothelium

Altered endothelial cell function is a key factor associated with vascular disorders and is critical in the fetal growth and development. Pregnancies affected by diseases such as gestational diabetes are associated with human umbilical vein endothelial dysfunction, a finding that has been associated with a high incidence of vascular complications during the adult life. Limited information is available addressing cellular mechanisms associated with altered human umbilical vein endothelial function in gestational diabetes. One of the key signalling pathways associated with altered vascular physiology is the synthesis of the vasodilator nitric oxide (NO) from the cationic amino acid L-arginine by the endothelium (i.e. the endothelial L-arginine/NO pathway). The activity of this signalling pathway is modulated by D-glucose, adenosine, insulin, and ATP, among other molecules, and is upregulated (transcriptional, post-transcriptional and post-translational levels) in gestational diabetes. This review focuses on the cellular and molecular mechanisms involved with elevated adenosine levels in fetal umbilical vein blood and the endothelial L-arginine/NO pathway activity in gestational diabetes. We suggest that a lower capacity of adenosine transport by the fetal endothelium in gestational diabetes leads to extracellular accumulation of this nucleoside and its higher bio-availability activates endothelial P1 type purinoceptors. A functional association between A2a purinoceptor subtype signalling and the activity of the l-arginine transport mediated by human cationic amino acid transporters and endothelial NO synthase activity (i.e. 'ALANO pathway') is proposed, revealing in part the mechanisms that account for human umbilical vein endothelial cell dysfunction programmed through the development of the fetus in gestational diabetes.