MicroRNA-1185 Induces Endothelial Cell Apoptosis by Targeting UVRAG and KRIT1

Background/Aims: Atherosclerosis is a multifactorial chronic disease and is the main cause of death and impairment in the world. Endothelial injury and apoptosis play a crucial role in the onset and development of atherosclerosis. MicroRNAs (miRNAs) have been proven to be involved in the pathogenesis of atherosclerosis. However, studies of the functional role of apoptosis-related miRNAs in the endothelium during atherogenesis are limited. Methods: Cell injury and apoptosis were measured in five types of cells transfected with miR-1185 or co-transfected with miR-1185 and its inhibitor. Bioinformatics analysis and a luciferase reporter assay were used to confirm the targets of miR-1185. The effects of the targets of miR-1185 on endothelial apoptosis were determined using small-interfering RNA. Results: In this study, we first report that miR-1185 significantly promoted apoptosis in endothelial cells but not in vascular smooth muscle cells and macrophages. A mechanistic analysis showed that ultraviolet irradiation resistance-associated gene (UVRAG) and krev1 interaction trapped gene 1 (KRIT1), targets of miR-1185, mediated miR-1185-induced endothelial cell apoptosis. Conclusion: The results revealed the impact of miR-1185 on endothelial apoptosis, suggesting that miR-1185 may be a potential target for the prevention and treatment of atherosclerosis.

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LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis

Molecular Medicine ◽

10.1186/s10020-020-00228-5 ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Zhimin Zhang ◽

Mingzhu Lv ◽

Xiang Wang ◽

Zheng Zhao ◽

Daolong Jiang ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Cell Apoptosis ◽

Critical Role ◽

Potential Interaction ◽

Luciferase Reporter ◽

Endothelial Cell Apoptosis ◽

Luciferase Activity Assay ◽

Apoptosis Related Protein

Abstract Background The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis. Methods Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting. Results Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR-195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis. Conclusion In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis.

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

Cellular Physiology and Biochemistry ◽

10.1159/000438511 ◽

2015 ◽

Vol 37 (4) ◽

pp. 1421-1430 ◽

Cited By ~ 17

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.

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Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis

Cellular and Molecular Life Sciences ◽

10.1007/s00018-018-2983-9 ◽

2018 ◽

Vol 76 (6) ◽

pp. 1093-1106 ◽

Cited By ~ 39

Author(s):

Stephanie Paone ◽

Amy A. Baxter ◽

Mark D. Hulett ◽

Ivan K. H. Poon

Keyword(s):

Endothelial Cell ◽

Extracellular Vesicles ◽

Cell Apoptosis ◽

Endothelial Cell Apoptosis ◽

Progression Of Atherosclerosis

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IL-17B Regulates Endothelial Cell Apoptosis in Venous Thrombosis

Nanoscience and Nanotechnology Letters ◽

10.1166/nnl.2020.3212 ◽

2020 ◽

Vol 12 (9) ◽

pp. 1106-1113

Author(s):

Yunyan Li ◽

Yuan Yang ◽

Jianfu Chen ◽

Yuxue Wang ◽

Yong Zhang ◽

...

Keyword(s):

Endothelial Cell ◽

Venous Thrombosis ◽

Cell Apoptosis ◽

Thrombus Formation ◽

Vascular Endothelial Cell ◽

Public Health Problem ◽

Vascular Wall ◽

Interleukin 17 ◽

Endothelial Cell Apoptosis ◽

Endothelial Apoptosis

Venous thromboembolism (VTE) is the comorbidity of deep vein thrombosis (DVT) and pulmonary embolism (PE); it is an urgent public health problem. The primary cause of venous thrombosis is endothelial dysfunction caused by vascular injury and inflammation or overexpressed procoagulant factors. Previous studies have shown that vascular endothelial cell apoptosis is involved in venous thrombosis, causing vascular wall damage. The pro-inflammatory cytokine interleukin-17 (Il-17A) induces endothelial cell apoptosis and promotes thrombosis. However, it remains unclear whether other IL-17 family cytokines are involved in thrombus formation. Among the IL-17 family, IL-17B is less well-characterized. Several studies have reported that IL-17B could stimulate TNF-α, IL-1, and IL-6 expression in macrophages. Furthermore, IL-17B induced activation of the ERK1/2 pathway, upregulating Bcl-2 family anti-apoptotic proteins in breast tumors. However, it is unclear whether IL-17B is involved in thrombus formation by regulating endothelial apoptosis. Therefore, this study aimed to examine whether IL-17B could affect endothelial apoptosis by promoting thrombus formation.

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Oxidized LDL-induced endothelial cell apoptosis: Role of mediator phospholipids and bFGF

Atherosclerosis ◽

10.1016/s0021-9150(00)80981-8 ◽

2000 ◽

Vol 151 (1) ◽

pp. 215-216

Author(s):

C. Chen ◽

J. Yang ◽

S. Luo ◽

P. Chang ◽

R. Gross ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Apoptosis ◽

Oxidized Ldl ◽

Endothelial Cell Apoptosis

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Cytosolic phospholipase A2-α is an early apoptotic activator in PEDF-induced endothelial cell apoptosis

AJP Cell Physiology ◽

10.1152/ajpcell.00432.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. C273-C284 ◽

Cited By ~ 18

Author(s):

Tsung-Chuan Ho ◽

Show-Li Chen ◽

Yuh-Cheng Yang ◽

Tzu-Hsiu Lo ◽

Jui-Wen Hsieh ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

P38 Mapk ◽

Cell Apoptosis ◽

Nuclear Translocation ◽

Mitogen Activated Protein Kinase ◽

Endothelial Cell Apoptosis ◽

P53 Expression ◽

Ppar Γ

Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor and a potential therapeutic agent. Previously, we discovered the mechanism of PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as sequential induction/activation of p38 mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), and p53. In the present study, we investigated the signaling role of cytosolic calcium-dependent phospholipase A2-α (cPLA2-α) to bridge p38 MAPK and PPAR-γ activation. PEDF induced cPLA2-α activation in HUVECs and in endothelial cells in chemical burn-induced vessels on mouse cornea. The cPLA2-α activation is evident from the phosphorylation and nuclear translocation of cPLA2-α as well as arachidonic acid release and the cleavage of PED6, a synthetic PLA2 substrate. Such activation can be abolished by p38 MAPK inhibitor. The PEDF-induced PPAR-γ activation, p53 expression, caspase-3 activity, and apoptosis can be abolished by both cPLA2 inhibitor and small interfering RNA targeting cPLA2-α. Our observation not only establishes the signaling role of cPLA2-α but also for the first time demonstrates the sequential activation of p38 MAPK, cPLA2-α, PPAR-γ, and p53 as the mechanism of PEDF-induced endothelial cell apoptosis.

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