scholarly journals UNC5B Promotes Vascular Endothelial Cell Senescence via the ROS-Mediated P53 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zhen Yang ◽  
Han Li ◽  
Pengcheng Luo ◽  
Dan Yan ◽  
Ni Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Cell Number ◽  
Cell Senescence ◽  
Vascular Endothelial ◽  
Vascular Disorders ◽  
P53 Pathway ◽  
Age Related

Vascular endothelial cell senescence is involved in human aging and age-related vascular disorders. Guidance receptor UNC5B is implicated in oxidative stress and angiogenesis. Nonetheless, little is known about the role of UNC5B in endothelial cell senescence. Here, we cultured primary human umbilical vein endothelial cells to young and senescent phases. Subsequently, the expression of UNC5B was identified in replicative senescent cells, and then, its effect on endothelial cell senescence was confirmed by UNC5B-overexpressing lentiviral vectors and RNA interference. Overexpression of UNC5B in young endothelial cells significantly increased senescence-associated β-galactosidase-positive cells, upregulated the mRNAs expression of the senescence-associated secretory phenotype genes, reduced total cell number, and inhibited the potential for cell proliferation. Furthermore, overexpression of UNC5B promoted the generation of intracellular reactive oxygen species (ROS) and activated the P53 pathway. Besides, overexpression of UNC5B disturbed endothelial function by inhibiting cell migration and tube formation. Nevertheless, silencing UNC5B generated conflicting outcomes. Blocking ROS production or inhibiting the function of P53 rescued endothelial cell senescence induced by UNC5B. These findings suggest that UNC5B promotes endothelial cell senescence, potentially by activating the ROS-P53 pathway. Therefore, inhibiting UNC5B might reduce endothelial cell senescence and hinder age-related vascular disorders.

scholarly journals Proteome-Scale Profiling Reveals MAFG and MAFF as Two Novel Candidate Key Transcription Factors Involved in Palmitic acid Induced Umbilical Vein Endothelial Cells Apoptosis

2020 ◽  
Author(s):  
Mangyuan Wang ◽  
Fen Liu ◽  
Binbin Fang ◽  
Qiang Huo ◽  
Yining Yang
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
P Value ◽  
Vascular Endothelial ◽  
Endothelial Cell Apoptosis ◽  
Family Protein ◽  
Umbilical Vein Endothelial Cells

Abstract Backgrounds: Vascular endothelial cell apoptosis is the first risk factor of atherosclerosis (AS), and it can be induced by high doses of glucose and palmitic acid (PA). The purpose of our study is to use a new generation of high-throughput transcription factors (TFs) detecting method to identify novel candidate key TFs involved in PA-induced vascular endothelial cell apoptosis.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with 0µM PA (control group), 250µM PA (group 1), or 500µM PA (group 2). Candidate TFs among the three groups were determined by significant changes according to t-test, and pathway enrichment, western blot (WB) and RT-qPCR were then performed.Results: Fifty-one TFs showing with significant p value were identified, and 24 TFs with significant p value plus fold change > 2 and with dose-dependence were identified with 12 TFs biologically validated in former studies. Two of the remaining 12 novel TFs, v-maf musculoaponeurotic fibrosarcoma oncogene family protein G (MAFG) and v-maf musculoaponeurotic fibrosarcoma oncogene family protein F (MAFF), were matched to AS known signalling pathways and were validated by WB and RT-qPCR in our study.Conclusions: We identified MAFG and MAFF as novel candidate key TFs in vascular endothelial cell apoptosis, which is the key initial process of AS.

scholarly journals Anti-inflammatory Effect of Salvia Miltiorrhiza is Mediated via IL-6, JAK, and STAT Pathway in a Dysfunctional Vascular Endothelial Cell

2021 ◽  
Vol 8 (3) ◽  
pp. 1-12
Author(s):  
Emmanuel Adikwu Orgah
Keyword(s):  
Diabetes Mellitus ◽  
Signal Transduction ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Salvia Miltiorrhiza ◽  
Vascular Endothelial Cell ◽  
Vascular Complication ◽  
Vascular Endothelial ◽  
Extracellular Medium

The vascular complication of diabetes mellitus is a problem for the patient, and the ability to cope with the disease and the associated inflammation is a critical aspect of diabetes. Cytokines-induced inflammation in vascular endothelial cells (VECs) plays an active role in chronic diseases such as atherosclerosis, diabetes mellitus, kidney injury, and stroke. We investigated the role of total salvianolic acids (TSA), total tanshinones (TTSN), and their combination (TSA/TTSN) on the activated vascular endothelial cell and its inhibitory effect on signal transduction and cytokines regulation. In the extracellular medium of the injury model of human umbilical vein endothelial cells (HUVECs) induced by thrombin, the human IL-6, VCAM-1, and ICAM-1 were significantly elevated (p ˂ 0.05). However, suppression in the TSA, TTSN, and TSA/TTSN (100 µg/L)-treated groups (p > 0.05) were notable. TSA alone but not TTSN and TSA/TTSN combination, inhibited the expression of P-selectin (p < 0.05) and E-selectin (p < 0.01) respectively, in VECs. Western blot analysis showed JAK and STAT expression in VECs however, the protein expression was modest in the Salvia miltiorrhiza-treated groups, indicating the potential of TSA/TTSN in the inflammatory pathways of IL-6, JAK, and STAT signal transduction in endothelial cells (ECs). This study has made novel observations regarding the components of Salvia miltiorrhiza regulatory effect on cytokines in Vascular Biology. Keywords: Atherosclerosis; Cytokines; Diabetes mellitus; HUVECs; Inflammation; Salvia militiorrhiza.

scholarly journals miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2

2020 ◽  
Vol 52 (2) ◽  
pp. 180-191 ◽  
Author(s):  
Qiaoli Chen ◽  
Xiaoye Li ◽  
Lingjun Kong ◽  
Qing Xu ◽  
Zi Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Nuclear Factor Κb ◽  
Vascular Endothelial ◽  
Ros Production ◽  
Cell Dysfunction ◽  
Umbilical Vein Endothelial Cells

Abstract Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.

Pterostilbene and its nicotinate derivative ameliorated vascular endothelial senescence and elicited endothelium-dependent relaxations via activation of Sirtuin 1

2021 ◽  
Author(s):  
Lili Zhang ◽  
Jianwei Zheng ◽  
Xin Tie ◽  
Tong Lin ◽  
Wanqi Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Cardiovascular Diseases ◽  
Vascular Endothelial Cell ◽  
Cell Senescence ◽  
Sirtuin 1 ◽  
Clinical Implications ◽  
Vascular Endothelial ◽  
Resveratrol Analogues

Aim: Vascular endothelial cell senescence is a leading cause of age-associated diseases and cardiovascular diseases. Interventions and therapies targeting endothelial cell senescence and dysfunction would have important clinical implications. This study was aimed to evaluate the effect of 10 resveratrol analogues, including pterostilbene (Pts) and its derivatives, against endothelial senescence and dysfunction. Methods and Results: All the tested compounds at the concentrations from 10-9 M to 10-6 M did not show cytotoxicity in endothelial cells. Among the 10 resveratrol analogues, Pts and Pts nicotinate attenuated the expression of senescence-associated β-galactosidase, downregulated p21 and p53, and increased the production of NO in both angiotensin II and H2O2-induced endothelial senescence models. In addition, Pts and Pts nicotinate elicited endothelium-dependent relaxations. Pts and Pts nicotinate did not alter Sirtuin 1 (SIRT1) expression but enhanced its activity. Both Pts and Pts nicotinate have high binding activities with SIRT1. Inhibition of SIRT1 by sirtinol reversed the anti-senescent effects of Pts and Pts nicotinate. Conclusions: This study suggests that the Pts and Pts nicotinate ameliorated vascular endothelial senescence and elicited endothelium-dependent relaxations via activation of SIRT1. These two compounds maybe potential drugs for the treatment of cardiovascular diseases related to endothelial senescence and dysfunction.

scholarly journals The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Tomohisa Sakaue ◽  
Iori Sakakibara ◽  
Takahiro Uesugi ◽  
Ayako Fujisaki ◽  
Koh-ichi Nakashiro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Function ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Death Domain ◽  
Endothelial Cell Function

Abstract Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively. Knockdown of SPOP and CUL3 led to the upregulation of DAXX protein and downregulation of VEGFR2 levels. These levels were inversely correlated with one another. In addition, simultaneous knockdown of SPOP and DAXX completely reversed the downregulation of VEGFR2 levels. Moreover, the CUL3-SPOP-DAXX axis had the same effects on NOTCH1, DLL4 and NRP1 expression. Taken together, these findings suggest that the CUL3-SPOP-DAXX axis plays a very important role in endothelial cell function by targeting key angiogenic regulators.

scholarly journals Fluidization, resolidification, and reorientation of the endothelial cell in response to slow tidal stretches

2012 ◽  
Vol 303 (4) ◽  
pp. C368-C375 ◽  
Author(s):  
Ramaswamy Krishnan ◽  
Elizabeth Peruski Canović ◽  
Andreea L. Iordan ◽  
Kavitha Rajendran ◽  
Greeshma Manomohan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Mechanical Stretch ◽  
Vascular Endothelial ◽  
Cell Mapping ◽  
Traction Forces ◽  
Morphological Response ◽  
Umbilical Vein Endothelial Cells

Mechanical stretch plays an important role in regulating shape and orientation of the vascular endothelial cell. This morphological response to stretch is basic to angiogenesis, neovascularization, and vascular homeostasis, but mechanism remains unclear. To elucidate mechanisms, we used cell mapping rheometry to measure traction forces in primary human umbilical vein endothelial cells subjected to periodic uniaxial stretches. Onset of periodic stretch of 10% strain amplitude caused a fluidization response typified by attenuation of traction forces almost to zero. As periodic stretch continued, the prompt fluidization response was followed by a slow resolidification response typified by recovery of the traction forces, but now aligned along the axis perpendicular to the imposed stretch. Reorientation of the cell body lagged reorientation of the traction forces, however. Together, these observations demonstrate that cellular reorientation in response to periodic stretch is preceded by traction attenuation by means of cytoskeletal fluidization and subsequent traction recovery transverse to the stretch direction by means of cytoskeletal resolidification.

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

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