Effect of simvastatin on endothelial cell apoptosis mediated by Fas and TNF-α

This study investigated the frequency of apoptosis in rat pulmonary artery endothelial cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO), tumour necrosis factor alpha (TNF-α ), and vascular endothelial growth factor (VEGF) in nicotine-induced vascular damage and the protective effects of two known antioxidant agents, N-acetylcysteine (NAC) and vitamin E. Female Wistar rats were divided into four groups, each composed of nine rats: negative control group, positive control group, NACtreated group (500 mg/kg), and vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. Apoptosis level in endothelial cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-α and VEGF in endothelial cells, and perivascular MPO activity were evaluated by immunohistochemistry. The treatments with NAC and vitamin E significantly reduced the rate of nicotine-induced endothelial cell apoptosis. NAC and vitamin E significantly reduced the increases in the local production of TNF-α and VEGF, and perivascular MPO activity. This findings suggest that NAC can be as effective as vitamin E in protecting against nicotine-induced endothelial cell apoptosis. Human & Experimental Toxicology (2007) 26: 595—602.

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Differential effect of MLC kinase in TNF-α-induced endothelial cell apoptosis and barrier dysfunction

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.280.6.l1168 ◽

2001 ◽

Vol 280 (6) ◽

pp. L1168-L1178 ◽

Cited By ~ 147

Author(s):

Irina Petrache ◽

Alexander D. Verin ◽

Michael T. Crow ◽

Anna Birukova ◽

Feng Liu ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Apoptosis ◽

Electrical Resistance ◽

Stress Fiber ◽

Fiber Formation ◽

Endothelial Cell Apoptosis ◽

Gap Formation ◽

Barrier Dysfunction ◽

Tnf Α ◽

Mlc Phosphorylation

Tumor necrosis factor (TNF)-α is released in acute inflammatory lung syndromes linked to the extensive vascular dysfunction associated with increased permeability and endothelial cell apoptosis. TNF-α induced significant decreases in transcellular electrical resistance across pulmonary endothelial cell monolayers, reflecting vascular barrier dysfunction (beginning at 4 h and persisting for 48 h). TNF-α also triggered endothelial cell apoptosis beginning at 4 h, which was attenuated by the caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone. Exploring the involvement of the actomyosin cytoskeleton in these important endothelial cell responses, we determined that TNF-α significantly increased myosin light chain (MLC) phosphorylation, with prominent stress fiber and paracellular gap formation, which paralleled the onset of decreases in transcellular electrical resistance and enhanced apoptosis. Reductions in MLC phosphorylation by the inhibition of either MLC kinase (ML-7, cholera toxin) or Rho kinase (Y-27632) dramatically attenuated TNF-α-induced stress fiber formation, indexes of apoptosis, and caspase-8 activity but not TNF-α-induced barrier dysfunction. These studies indicate a central role for the endothelial cell cytoskeleton in TNF-α-mediated apoptosis, whereas TNF-α-induced vascular permeability appears to evolve independently of contractile tension generation.

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Effects and mechanism of arachidonic acid against TNF-α induced apoptosis of endothelial cells

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-200946 ◽

2020 ◽

pp. 1-7

Author(s):

Ji-Xiong Chen ◽

Xiao-Yan Huang ◽

Ping Wang ◽

Wen-Ting Lin ◽

Wen-Xing Xu ◽

...

Keyword(s):

Flow Cytometry ◽

Endothelial Cells ◽

Arachidonic Acid ◽

Endothelial Cell ◽

Cell Apoptosis ◽

Umbilical Vein ◽

Arachidonic Acid Metabolite ◽

Apoptotic Cells ◽

Endothelial Cell Apoptosis ◽

Tnf Α

This study aimed to investigate the effects of arachidonic acid metabolite epoxyeicosatrienoic acid (EETs) in the apoptosis of endothelial cells induced by tumor necrosis factor-alpha (TNF-α). After human umbilical vein endothelial cells were cultured, TNF-α/ActD, 14, 15-EET, and HMR-1098 were added, respectively, into the culture medium. The apoptosis level of endothelial cells was detected by flow cytometry. After TNF-α/ActD induced endothelial cell apoptosis, flow cytometry staining showed that endothelial cell apoptosis increased significantly, and the apoptotic cells were significantly reduced after the addition of 14, 15-EET. However, the apoptotic cells significantly increased after the addition of HMR-1098. Western Blot results showed that the phosphorylation levels of LC3-II and AMPK were increased after TNF-α/ActD induction, and the increase was noticeable after the addition of 14, 15-EET. However, the phosphorylation levels of LC3-II and AMPK significantly decreased after the addition of HMR-1098. The activity of Caspase-8 and -9 decreased significantly after the addition of 14, 15-EET but increased after the addition of HMR-1098. Arachidonic acid can inhibit TNF-α induced endothelial cell apoptosis by upregulating autophagy.

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IGFBP-3 and TNF-α Regulate Retinal Endothelial Cell Apoptosis

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.13-12497 ◽

2013 ◽

Vol 54 (8) ◽

pp. 5376 ◽

Cited By ~ 22

Author(s):

Qiuhua Zhang ◽

Youde Jiang ◽

Matthew J. Miller ◽

Bonnie Peng ◽

Li Liu ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Apoptosis ◽

Endothelial Cell Apoptosis ◽

Tnf Α ◽

Retinal Endothelial Cell ◽

Igfbp 3

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Role of protein kinase C β2 activation in TNF-α-induced human vascular endothelial cell apoptosis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y09-004 ◽

2009 ◽

Vol 87 (3) ◽

pp. 221-229 ◽

Cited By ~ 12

Author(s):

Fang Wang ◽

Hui-min Liu ◽

Michael G. Irwin ◽

Zhong-yuan Xia ◽

Zhiyong Huang ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Cell Apoptosis ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Vascular Endothelial ◽

Endothelial Cell Apoptosis ◽

Human Vascular Endothelial Cell ◽

Kinase C ◽

Tnf Α

The circulatory inflammatory cytokine tumor necrosis factor alpha (TNF-α) is increased in pathologic conditions that initiate or exacerbate vascular endothelial injury, such as diabetes. Protein kinase C (PKC) has been shown to play a critical role in TNF-α-induced human endothelial cell apoptosis. However, the relative roles played by specific isoforms of PKC in TNF-α-induced human endothelial cell apoptosis have not been addressed. We investigated the effects of a selective PKCβ2 inhibitor (CGP53353) on TNF-α-induced apoptosis in human vascular endothelial cells (cell line ECV304) and on the production of reactive oxygen species and nitric oxide, and compared its effects with rottlerin, a reagent that has been shown to reduce PKCδ protein levels. Cultured human vascular endothelial cells (ECV304) were treated for 24 h with one of 4 regimes: 40 ng/mL TNF-α alone (TNF-α), TNF-α with 10 µmol/L rottlerin (T+rottlerin), TNF-α with 1 µmol/L CGP53353 (T+CGP), or untreated (control). Cell viability was measured by MTT assay, and cell apoptosis was assessed by flow cytometry. TNF-α-induced endothelial cell apoptosis was associated with dramatic increases in production of intracellular hydrogen peroxide (approximately 20 times greater than control) and superoxide (approximately 16 times greater than control), as measured by dichlorofluorescein and dihydroethidium fluorescent staining, respectively. This increase was accompanied by reduced activity of superoxide dismutase and glutathione peroxidase and, subsequently, an increase in the lipid peroxidation product malondialdehyde. CGP53353, but not rottlerin, abolished or attenuated all these changes. We conclude that PKCβ2 plays a major role in TNF-α-induced human vascular endothelial cell apoptosis.

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