scholarly journals Docetaxel causes lymphatic endothelial cell apoptosis and impairs lymphatic function and gene expression in vitro

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Wong AM ◽  
Baik JE ◽  
Park H ◽  
Li C ◽  
Shin JY ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Lymphatic Endothelial Cell ◽  
Endothelial Cell Apoptosis ◽  
Lymphatic Function

In vitro induction of microglial and endothelial cell apoptosis by cerebrospinal fluids from patients with human African trypanosomiasis

2003 ◽  
Vol 33 (7) ◽  
pp. 713-720 ◽  
Author(s):  
Murielle Girard ◽  
Sylvie Bisser ◽  
Bertrand Courtioux ◽  
Claudine Vermot-Desroches ◽  
Bernard Bouteille ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Human African Trypanosomiasis ◽  
African Trypanosomiasis ◽  
Endothelial Cell Apoptosis ◽  
In Vitro Induction

scholarly journals Atherosclerosis-Associated Endothelial Cell Apoptosis by MiR-429-Mediated Down Regulation of Bcl-2

2015 ◽  
Vol 37 (4) ◽  
pp. 1421-1430 ◽  
Author(s):  
Tao Zhang ◽  
Feng Tian ◽  
Jing Wang ◽  
Jing Jing ◽  
Shan-Shan Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Luciferase Reporter ◽  
Lower Percentage ◽  
Endothelial Cell Apoptosis ◽  
Down Regulation ◽  
Bioinformatics Analyses

Background/Aims: Endothelial cell injury and subsequent apoptosis play a key role in the development and pathogenesis of atherosclerosis, which is hallmarked by dysregulated lipid homeostasis, aberrant immunity and inflammation, and plaque-instability-associated coronary occlusion. Nevertheless, our understanding of the mechanisms underlying endothelial cell apoptosis is still limited. MicroRNA-429 (miR-29) is a known cancer suppressor that promotes cancer cell apoptosis. However, it is unknown whether miR-429 may be involved in the development of atherosclerosis through similar mechanisms. We addressed these questions in the current study. Methods: We examined the levels of endothelial cell apoptosis in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of anti-apoptotic protein Bcl-2 and the levels of miR-429 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-429 and 3'-UTR of Bcl-2 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-429 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. HFD mice had significantly lower percentage of endothelial cells and significantly higher percentage of mesenchymal cells in the aorta than NOR mice. Significantly higher levels of endothelial cell apoptosis were detected in HFD mice, resulting from decreases in Bcl-2 protein, but not mRNA. The decreases in Bcl-2 in endothelial cells were due to increased levels of miR-429, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Atherosclerosis-associated endothelial cell apoptosis may result from down regulation of Bcl-2, through increased miR-429 that binds and suppresses translation of Bcl-2 mRNA.

scholarly journals Upregulation of microRNA-876 Induces Endothelial Cell Apoptosis by Suppressing Bcl-Xl in Development of Atherosclerosis

2017 ◽  
Vol 42 (4) ◽  
pp. 1540-1549 ◽  
Author(s):  
Kaicheng Xu ◽  
Peng Liu ◽  
Yue Zhao
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Aortic Arch ◽  
Cell Apoptosis ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Luciferase Reporter ◽  
Endothelial Cell Apoptosis

Background/Aims: The injury and apoptotic cell death of endothelial cells hallmark the development of atherosclerosis (AS), characterized by dysregulation of lipid homeostasis, immune responses, and formation of coronary plaques. However, the mechanisms underlying the initiation of endothelial cell apoptosis remain ill-defined. Recent evidence suggests a role of microRNAs in the processes of AS-associated endothelial cell apoptosis. Thus, we studied this question in the current study. Methods: AS was developed in ApoE (-/-) mice suppled with high-fat diet (HFD), compared to ApoE (-/-) mice suppled with normal diet (ND). Mouse endothelial cells were isolated from the aortic arch using flow cytometry based on their expression of Pecam-1. Oxidized low-density lipoprotein (ox-LDL) were used to treat human aortic endothelial cells (HAECs) as an in vitro model for AS. Gene expression was quantified by RT-qPCR and protein levels were analyzed by Western blotting. Apoptosis was evaluated by FITC Annexin V Apoptosis essay and by TUNEL staining. Prediction of the binding between miRNAs and 3'-UTR of mRNA from the target gene was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. Results: HFD mice, but not ND mice, developed AS in 12 weeks. Significantly reduced endothelial cell marks and significantly increased mesenchymal cell marks were detected in the aortic arch of the HFD mice, compared to the ND mice. The endothelial cell apoptosis was significantly higher in HFD mice, seemingly due to functional suppression of protein translation of anti-apoptotic Bcl-Xl protein through upregulation of miR-876. Similar results were obtained from in vitro study. Inhibition of miR-876 abolished the effects of ox-LDL-induced apoptotic cell death of HAECs. Conclusion: AS-associated endothelial cell apoptosis may partially result from downregulation of Bcl-Xl, through upregulation of miR-876 that binds and suppresses translation of Bcl-Xl mRNA.

FRP inhibits ox-LDL-induced endothelial cell apoptosis through an Akt-NF-κB-Bcl-2 pathway and inhibits endothelial cell apoptosis in an apoE-knockout mouse model

2010 ◽  
Vol 299 (3) ◽  
pp. E351-E363 ◽  
Author(s):  
Shu Liu ◽  
Hua Shen ◽  
Ming Xu ◽  
Ou Liu ◽  
Limin Zhao ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Endothelial Damage ◽  
Endothelial Cell Apoptosis ◽  
Knockout Mouse Model ◽  
Apoe Knockout Mouse

Atherosclerosis is the most common cause of cardiovascular diseases in the world. Although the development of atherosclerosis appears to be the result of multiple maladaptive pathways, a particularly important factor in the pathogenesis of atherosclerosis is oxidized low-density lipoprotein (ox-LDL), which contributes to endothelial damage. Data from our laboratory and others show that follistatin-related protein (FRP), which is expressed in the vasculature, has cardioprotective effects, suggesting that loss of FRP protection might play a role in the development of atherosclerosis. In the present study, we determined whether FRP overexpression protects against endothelial cell (EC) damage, an intermediate end point for atherosclerosis. We bred apoE-knockout (apoE−/−) mice that were FRP+ transgenic (they overexpressed FRP). We compared them with control mice (their littermates). Human umbilical vein endothelial cells (HUVECs) were isolated and treated with ox-LDL and recombinant FRP. FRP-induced signal transduction and Bcl-2 mRNA and protein stability were analyzed. After 16 wk, apoE−/− FRP+ mice had significantly fewer apoptotic ECs than controls. In vitro experiments showed that the effect of FRP on EC apoptosis was mediated by upregulation of expression of the antiapoptotic protein Bcl-2. In HUVECs, FRP upregulated Bcl-2 transcription via a PI3K-Akt-NF-κB pathway. We conclude that FRP overexpression maintains EC viability by preventing apoptosis via Bcl-2 upregulation. FRP may be a novel therapeutic target for the prevention and treatment of vascular EC injury and of atherosclerosis.

Mast cell-mediated downregulation of Bcl-2 expression triggers endothelial cell apoptosis in vitro

2000 ◽  
Vol 151 (1) ◽  
pp. 216
Author(s):  
S. Lätti ◽  
N. Shiota ◽  
M. Leskinen ◽  
Y. Wang ◽  
P. Kovanen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Endothelial Cell Apoptosis

Hyperoxia induces retinal vascular endothelial cell apoptosis through formation of peroxynitrite

2003 ◽  
Vol 285 (3) ◽  
pp. C546-C554 ◽  
Author(s):  
Xiaolin Gu ◽  
Azza B. El-Remessy ◽  
Steven E. Brooks ◽  
Mohamed Al-Shabrawey ◽  
Nai-Tsi Tsai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cell ◽  
In Vivo Studies ◽  
Endothelial Cell Apoptosis ◽  
Akt Kinase ◽  
Induced Apoptosis

Hyperoxia exposure induces capillary endothelial cell apoptosis in the developing retina, leading to vaso-obliteration followed by proliferative retinopathy. Previous in vivo studies have shown that endothelial nitric oxide synthase (NOS3) and peroxynitrite are important mediators of the vaso-obliteration. Now we have investigated the relationship between hyperoxia, NOS3, peroxynitrite, and endothelial cell apoptosis by in vitro experiments using bovine retinal endothelial cells (BREC). We found that BREC exposed to 40% oxygen (hyperoxia) for 48 h underwent apoptosis associated with activation of caspase-3 and cleavage of the caspase substrate poly(ADP-ribose) polymerase. Hyperoxia-induced apoptosis was associated with increased formation of nitric oxide, peroxynitrite, and superoxide anion and was blocked by treatment with uric acid, nitro-l-arginine methyl ester, or superoxide dismutase. Analyses of the phosphatidylinositol 3-kinase/Akt kinase survival pathway in cells directly treated with peroxynitrite revealed inhibition of VEGF- and basic FGF-induced activation of Akt kinase. These results suggest that hyperoxia-induced formation of peroxynitrite induces BREC apoptosis by crippling key survival pathways and that blocking peroxynitrite formation prevents apoptosis. These data may have important clinical implications for infants at risk of retinopathy of prematurity.

scholarly journals DAXX mediates high phosphate-induced endothelial cell apoptosis in vitro through activating ERK signaling

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9203
Author(s):  
Shu Wang ◽  
Mingyu Wu ◽  
Ling Qin ◽  
Yaxiang Song ◽  
Ai Peng
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Kidney Diseases ◽  
Umbilical Vein ◽  
Additional Treatment ◽  
Erk Signaling ◽  
Death Domain ◽  
Endothelial Cell Apoptosis

Backgroud and Purpose Hyperphosphatemia, which is a high inorganic phosphate (Pi) level in the serum, promotes endothelial cells dysfunction and is associated with cardiovascular diseases in patients with chronic kidney diseases (CKD). However, the underlying mechanism of high Pi-induced endothelia cell apoptosis remains unclear. Methods Human umbilical vein endothelial cells (HUVECs) were treated with normal Pi (1.0 mM) and high Pi (3.0 mM), and then cell apoptosis, abnormal gene expression and potential signaling pathway involvement in simulated hyperphosphatemia were examined using flow cytometry, quantitative PCR (qPCR) and western blot analysis. A two-step 5/6 nephrectomy was carried out to induce CKD and biochemical measurements were taken. Results The rat model of CKD revealed that hyperphosphatemia is correlated with an increased death-domain associated protein (DAXX) expression in endothelial cells. In vitro, high Pi increased the mRNA and protein expression level of DAXX in HUVECs, effects that were reversed by additional phosphonoformic acid treatment. Functionally, high Pi resulted in a significantly increased apoptosis in HUVECs, whereas DAXX knockdown markedly repressed high Pi-induced cell apoptosis, indicating that DAXX mediated high Pi-induced endothelial cell apoptosis. High Pi treatment and DAXX overexpression induced the activation of extracellular regulated protein kinases (ERKs), while DAXX knockdown inhibited high Pi-induced ERKs activation. Finally, we demonstrated that DAXX overexpression induced HUVECs apoptosis in the presence of normal Pi, whereas additional treatment with U0126 (a specific ERK inhibitor) reversed that effect. Conclusion Upregulated DAXX promoted high Pi-induced HUVECs apoptosis by activating ERK signaling and indicated that the DAXX/ERK signaling axis may be served as a potential target for CKD therapy.

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