Amorphous Selenium Nanoparticles Improve Vascular Function in Rats With Chronic Isocarbophos Poisoning via Inhibiting the Apoptosis of Vascular Endothelial Cells

AimThis study aimed to investigate the preventive effect and possible mechanism of amorphous selenium nanoparticles (A-SeQDs) on isocarbophos induced vascular dysfunction.MethodsA-SeQDs was made by auto redox decomposition of selenosulfate precursor. Male rats were given isocarbophos (0.5 mg/kg/2 days) by intragastric administration for 16 weeks to induce vascular dysfunction. During the course, A-SeQDs (50 mg/kg/day) was added to the water from week 5. Then, the rats were killed to observe and test the influence of A-SeQDs on the vascular dysfunction induced by isocarbophos. Finally, human umbilical vein endothelial cells (HUVECs) were treated with 10% DMEM of isocarbophos (100 μM) for 5 days to detect the related indexes. Before the use of isocarbophos treatment, different drugs were given.ResultsA-SeQDs could reduce total carbon dioxide, MDA, VCAM-1, ICAM-1, IL-1, and IL-6 while increasing oxygen saturation, NO content, and SOD activity in rats. A-SeQDs also resulted in relatively normal vascular morphology, and the expression of sodium hydrogen exchanger 1 (NHE1) and caspase-3 decreased in rats. Furthermore, in HUVECs treated with isocarbophos, A-SeQDs maintained mitochondrial membrane potential, inhibited the cleaved caspase-3 expression, and released cytochrome c from mitochondria to cytosol.ConclusionA-SeQDs can inhibit the apoptosis of HUVECs through the mitochondrial pathway, and effectively treat the impairment of vascular endothelial function caused by isocarbophos, which is NHE1-dependent.

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Immobilized DNA aptamers used as potent attractors for vascular endothelial cell: in vitro study of female rat

Bioscience Reports ◽

10.1042/bsr20182444 ◽

2020 ◽

Vol 40 (1) ◽

Cited By ~ 1

Author(s):

Jung-Joon Cha ◽

Hoyeon Lee ◽

Miyoung Kim ◽

Juyoung Kang ◽

Hanlim Song ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Function ◽

Therapeutic Potential ◽

Vascular Endothelial Cells ◽

Specific Binding ◽

Vascular Endothelial Cell ◽

Dna Aptamers ◽

Female Rat ◽

Vascular Endothelial

Abstract Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

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Abstract 14820: Sirt7 Deficiency in Blood Vessel Components Impairs Vascular Function by Inhibiting Cell Cycle- and Inflammatory-Related Protein Expression

Circulation ◽

10.1161/circ.132.suppl_3.14820 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yuichi Kimura ◽

Yasuhiro Izumiya ◽

Satoshi Araki ◽

Satoru Yamamura ◽

Yoshiro Onoue ◽

...

Keyword(s):

Cell Proliferation ◽

Endothelial Cells ◽

Blood Flow ◽

Vascular Function ◽

Vascular Dysfunction ◽

Vascular Diseases ◽

Tube Formation ◽

Hindlimb Ischemia ◽

Proliferation Assay

Introduction: Aging is a well-established cardiovascular risk factor and associated with vascular dysfunction. Sirt7, one of the members of mammalian sirtuin family, is thought to be involved in age-related diseases. However, little is known about the relative contribution of Sirt7 in vascular dysfunction. Hypothesis: Sirt7 maintains vascular cell functions and its deficiency plays a critical role in vascular diseases. Methods: Sirt7 loss- and gain-of-function experiments were performed with human aortic smooth muscle cells (HAoSMCs) and human umbilical vein endothelial cells (HUVECs). In vivo, blood flow recovery was evaluated by hindlimb ischemia model in homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Irradiated WT mice were intravenously received bone marrow (BM) cells from WT or Sirt7 -/- mouse to achieve BM transfer. Results: An RNAi-medicated Sirt7 knockdown resulted in a significant inhibition of HAoSMCs proliferation following serum or Platelet-derived growth factor BB (PDGF-BB) stimulation as determined by cell count, BrdU cell proliferation assay and MTS proliferation assay. Knockdown of endogenous Sirt7 also reduced cell migration as revealed by Boyden chamber migration assay. The Cyclin D1 and Cyclin dependent kinase 2 (CDK2) protein levels were significantly decreased in Sirt7 siRNA-treated HAoSMCs in response to serum or PDGF-BB stimulation. In endothelial cells, knockdown of Sirt7 attenuated tube formation, proliferation and migration. These changes were accompanied by reduced ERK activation and VCAM-1 mRNA and protein expression in Sirt7 siRNA-treated HUVECs. Conversely, overexpression of Sirt7 by adenovirus enhanced tube formation and cell proliferation. In vivo, blood flow recovery in response to hindlimb ischemia was significantly attenuated in Sirt7-/- mice compared with WT mice. There was no difference in blood flow recovery between WT mice transplanted with WT or Sirt7-/- BM cells suggesting that Sirt7 deficiency in vascular cells have a predominant effect on attenuated blood flow recovery in response to hindlimb ischemia. Conclusions: Sirt7 in blood vessel components have an important role in maintenance of vascular function. Sirt7 could be a promising therapeutic target for vascular diseases.

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L-Cystathionine Protects against Homocysteine-Induced Mitochondria-Dependent Apoptosis of Vascular Endothelial Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1253289 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Xiuli Wang ◽

Yi Wang ◽

Lulu Zhang ◽

Da Zhang ◽

Lu Bai ◽

...

Keyword(s):

Endothelial Cells ◽

Caspase 3 ◽

Mitochondrial Permeability Transition ◽

Vascular Endothelial Cells ◽

Permeability Transition Pore ◽

Permeability Transition ◽

Vascular Endothelial ◽

Caspase 9 ◽

Mitochondrial Superoxide ◽

Mptp Opening

The study was aimed at investigating the effects of L-cystathionine on vascular endothelial cell apoptosis and its mechanisms. Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. Apoptosis of vascular endothelial cells was induced by homocysteine. Apoptosis, mitochondrial superoxide anion, mitochondrial membrane potential, mitochondrial permeability transition pore (MPTP) opening, and caspase-9 and caspase-3 activities were examined. Expression of Bax, Bcl-2, and cleaved caspase-3 was tested and BTSA1, a Bax agonist, and HUVEC Bax overexpression was used in the study. Results showed that homocysteine obviously induced the apoptosis of HUVECs, and this effect was significantly attenuated by the pretreatment with L-cystathionine. Furthermore, L-cystathionine decreased the production of mitochondrial superoxide anion and the expression of Bax and restrained its translocation to mitochondria, increased mitochondrial membrane potential, inhibited mitochondrial permeability transition pore (MPTP) opening, suppressed the leakage of cytochrome c from mitochondria into the cytoplasm, and downregulated activities of caspase-9 and caspase-3. However, BTSA1, a Bax agonist, or Bax overexpression successfully abolished the inhibitory effect of L-cystathionine on Hcy-induced MPTP opening, caspase-9 and caspase-3 activation, and HUVEC apoptosis. Taken together, our results indicated that L-cystathionine could protect against homocysteine-induced mitochondria-dependent apoptosis of HUVECs.

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Dehydroepiandrosterone Protects Vascular Endothelial Cells against Apoptosis through a Gαi Protein-Dependent Activation of Phosphatidylinositol 3-Kinase/Akt and Regulation of Antiapoptotic Bcl-2 Expression

Endocrinology ◽

10.1210/en.2006-1378 ◽

2007 ◽

Vol 148 (7) ◽

pp. 3068-3076 ◽

Cited By ~ 74

Author(s):

Dongmin Liu ◽

Hongwei Si ◽

Kathryn A. Reynolds ◽

Wei Zhen ◽

Zhenquan Jia ◽

...

Keyword(s):

Endothelial Cells ◽

Estrogen Receptor ◽

Vascular Function ◽

Vascular Endothelial Cells ◽

Specific Inhibitor ◽

Vascular Endothelial ◽

Phosphatidylinositol 3 Kinase ◽

Antiapoptotic Effect ◽

Dose Dependent ◽

Phosphatidylinositol 3

The adrenal steroid dehydroepiandrosterone (DHEA) may improve vascular function, but the mechanism is unclear. In the present study, we show that DHEA significantly increased cell viability, reduced caspase-3 activity, and protected both bovine and human vascular endothelial cells against serum deprivation-induced apoptosis. This effect was dose dependent and maximal at physiological concentrations (0.1–10 nm). DHEA stimulation of bovine aortic endothelial cells resulted in rapid and dose-dependent phosphorylation of Akt, which was blocked by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), the upstream kinase of Akt. Accordingly, inhibition of PI3K or transfection of the cells with dominant-negative Akt ablated the antiapoptotic effect of DHEA. The induced Akt phosphorylation and subsequent cytoprotective effect of DHEA were dependent on activation of Gαi proteins, but were estrogen receptor independent, because these effects were blocked by pertussis toxin but not by the estrogen receptor inhibitor ICI182,780 or the aromatase inhibitor aminoglutethimide. Finally, DHEA enhanced antiapoptotic Bcl-2 protein expression, its promoter activity, and gene transcription attributable to the activation of the PI3K/Akt pathway. Neutralization of Bcl-2 by antibody transfection significantly decreased the antiapoptotic effect of DHEA. These findings provide the first evidence that DHEA acts as a survival factor for endothelial cells by triggering the Gαi-PI3K/Akt-Bcl-2 pathway to protect cells against apoptosis. This may represent an important mechanism underlying the vascular protective effect of DHEA.

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Elimination of Vitamin D Receptor in Vascular Endothelial Cells Alters Vascular Function

Hypertension ◽

10.1161/hypertensionaha.114.03971 ◽

2014 ◽

Vol 64 (6) ◽

pp. 1290-1298 ◽

Cited By ~ 79

Author(s):

Wei Ni ◽

Stephanie W. Watts ◽

Michael Ng ◽

Songcang Chen ◽

Denis J. Glenn ◽

...

Keyword(s):

Vitamin D ◽

Endothelial Cells ◽

Vitamin D Receptor ◽

Vascular Function ◽

Vascular Endothelial Cells ◽

Vascular Endothelial

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Dihydrotestosterone protects human vascular endothelial cells from H2O2-induced apoptosis through inhibition of caspase-3, caspase-9 and p38 MAPK

European Journal of Pharmacology ◽

10.1016/j.ejphar.2010.06.039 ◽

2010 ◽

Vol 643 (2-3) ◽

pp. 254-259 ◽

Cited By ~ 23

Author(s):

Zhe-rong Xu ◽

Lin Hu ◽

Lin-fang Cheng ◽

Yun Qian ◽

Yun-mei Yang

Keyword(s):

Endothelial Cells ◽

P38 Mapk ◽

Caspase 3 ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Caspase 9 ◽

Induced Apoptosis

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Effect of Hyperglycemia on Epcs Function and Regenerative Ability

University of the Future: Re-Imagining Research and Higher Education ◽

10.29117/quarfe.2020.0216 ◽

2020 ◽

Author(s):

Hadeel Khalil Hendawi ◽

Dina Nehad Awartani ◽

Aya Ghoul ◽

Isra Marei

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Barrier Function ◽

Vascular Endothelial Cells ◽

Vascular Dysfunction ◽

Vascular Complications ◽

Cardiovascular Complications ◽

Diabetic Patients ◽

Vascular Endothelial ◽

Cell Functions

Diabetes induced hyperglycemia increases the risk of cardiovascular complications as it impacts vascular endothelial cells causing vascular dysfunction. Endothelial progenitor cells (EPCs) have been suggested to participate in the repair of vascular endothelial cells once they are impacted by hyperglycemia in diabetic patients. This research aims to test the EPC subtype blood outgrowth endothelial cells (BOECs) and their ability to survive and function under chronic hyperglycemic conditions. For that, we studied BOECs viability, response to shear stress, angiogenesis ability, and barrier function under normoglycemic (5.5mM) and hyperglycemic (25mM) conditions. The results have shown significant effects of chronic hyperglycemic conditions on cell proliferation (n=3, p<0.05), and migration (n=3, p<0.05) which were decreased when compared to control. Cells responses to shear stress were not affected under these conditions. There was a trend towards an increase in permeability as indicated by barrier function assays. The decrease in those endothelial cell functions might impact the repair mechanisms needed in diabetic patients to protect from vascular complications. Further investigations are required to establish therapeutic targets to improve EPCs repair function.

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Metabolic Reprogramming of Vascular Endothelial Cells: Basic Research and Clinical Applications

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.626047 ◽

2021 ◽

Vol 9 ◽

Author(s):

Hanlin Peng ◽

Xiuli Wang ◽

Junbao Du ◽

Qinghua Cui ◽

Yaqian Huang ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Function ◽

Cell Injury ◽

Vascular Endothelial Cells ◽

Basic Research ◽

Initial Response ◽

Vascular Wall ◽

Metabolic Reprogramming ◽

Vascular Endothelial ◽

Endocrine Organ

Vascular endothelial cells (VECs) build a barrier separating the blood from the vascular wall. The vascular endothelium is the largest endocrine organ, and is well-known for its crucial role in the regulation of vascular function. The initial response to endothelial cell injury can lead to the activation of VECs. However, excessive activation leads to metabolic pathway disruption, VEC dysfunction, and angiogenesis. The pathways related to VEC metabolic reprogramming recently have been considered as key modulators of VEC function in processes such as angiogenesis, inflammation, and barrier maintenance. In this review, we focus on the changes of VEC metabolism under physiological and pathophysiological conditions.

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Dehydroepiandrosterone Stimulates Endothelial Proliferation and Angiogenesis through Extracellular Signal-Regulated Kinase 1/2-Mediated Mechanisms

Endocrinology ◽

10.1210/en.2007-1125 ◽

2007 ◽

Vol 149 (3) ◽

pp. 889-898 ◽

Cited By ~ 54

Author(s):

Dongmin Liu ◽

Mary Iruthayanathan ◽

Laurie L. Homan ◽

Yiqiang Wang ◽

Lingling Yang ◽

...

Keyword(s):

Endothelial Cells ◽

Plasma Membrane ◽

Vascular Function ◽

Nuclear Translocation ◽

Vascular Endothelial Cell ◽

Vascular Endothelial ◽

Vascular Effect ◽

Endothelial Proliferation ◽

Ribosomal S6 Kinase

Dehydroepiandrosterone (DHEA) activates a plasma membrane receptor on vascular endothelial cells and phosphorylates ERK 1/2. We hypothesize that ERK1/2-dependent vascular endothelial proliferation underlies part of the beneficial vascular effect of DHEA. DHEA (0.1–10 nm) activated ERK1/2 in bovine aortic endothelial cells (BAECs) by 15 min, causing nuclear translocation of phosphorylated ERK1/2 and phosphorylation of nuclear p90 ribosomal S6 kinase. ERK1/2 phosphorylation was dependent on plasma membrane-initiated activation of Gi/o proteins and the upstream MAPK kinase because the effect was seen with albumin-conjugated DHEA and was blocked by pertussis toxin or PD098059. A 15-min incubation of BAECs with 1 nm DHEA (or albumin-conjugated DHEA) increased endothelial proliferation by 30% at 24 h. This effect was not altered by inhibition of estrogen or androgen receptors or nitric oxide production. There was a similar effect of DHEA to increase endothelial migration. DHEA also increased the formation of primitive capillary tubes of BAECs in vitro in solubilized basement membrane. These rapid DHEA-induced effects were reversed by the inhibition of either Gi/o-proteins or ERK1/2. Additionally, DHEA enhanced angiogenesis in vivo in a chick embryo chorioallantoic membrane assay. These findings indicate that exposure to DHEA, at concentrations found in human blood, causes vascular endothelial proliferation by a plasma membrane-initiated activity that is Gi/o and ERK1/2 dependent. These data, along with previous findings, define an important vascular endothelial cell signaling pathway that is activated by DHEA and suggest that this steroid may play a role in vascular function.

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