scholarly journals Alpha-Asarone Protects Endothelial Cells from Injury by Angiotensin II

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-Xia Shi ◽  
Jiajun Yang ◽  
Tao Yang ◽  
Yong-Liang Xue ◽  
Jun Liu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Cell Injury ◽  
Fluorescent Dyes ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Ang Ii ◽  
Versus Model

α-Asarone is the major therapeutical constituent ofAcorus tatarinowiiSchott. In this study, the potential protective effects ofα-asarone against endothelial cell injury induced by angiotensin II were investigatedin vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated withα-asarone (10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) atSer1177was determined by Western blotting.α-Asarone dose-dependently mitigated the Ang II-induced intracellular NO reduction (P<0.01versus model) and ROS production (P<0.01versus model). Furthermore, eNOS phosphorylation (Ser1177) by acetylcholine was significantly inhibited by Ang II, while pretreatment for 1 h withα-asarone partially prevented this effect (P<0.05versus model). Additionally, cell viability determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (105~114.5% versus control,P>0.05) was not affected after 24 h of incubation withα-asarone at 1–100 µmol/L. Therefore,α-asarone protects against Ang II-mediated damage of endothelial cells and may be developed to prevent injury to cardiovascular tissues.

Panax Quinquefolium L. Inhibits Thrombin-Induced Endothelin Release In Vitro

1999 ◽  
Vol 27 (03n04) ◽  
pp. 331-338 ◽  
Author(s):  
Chun-Su Yuan ◽  
Anoja S. Attele ◽  
Ji An Wu ◽  
Tasha K. Lowell ◽  
Zhenlun Gu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Vascular Endothelial Cells ◽  
Cell Damage ◽  
Umbilical Vein ◽  
American Ginseng ◽  
Protective Effects ◽  
Panax Quinquefolium

Endothelial cell damage is considered to be the initial step in the genesis of thrombosis and arteriosclerosis, the common precursors of cardiovascular disorders. In this study, we evaluated the protective effects of American ginseng or Panax quinquefolium L. extracts on endothelial cell injury, and investigated effects of ginseng extracts on thrombin-induced endothelin release using cultured human umbilical vein endothelial cells. We observed that when endothelial cells pretreated with 1, 10, and 100 μg/ml of Panax quinquefolium L. extracts were incubated for 4 and 24 hr with thrombin, the concentration of endothelin was significantly decreased in a concentration dependent, time related manner (at 4 hr, IC50 = 5.1 μg/ml; at 24 hr, IC50 = 6.2 μg/ml). We further evaluated the effects of NG-nitro-L-arginine (NLA), a nitric oxide (NO) synthetase inhibitor, on the activity of Panax quinquefolium L. extracts. Following pretreatment of cultured endothelial cells with NLA, the inhibition of thrombin-induced endothelin release by Panax quinquefolium L. was significantly reduced (P < 0.05). This result suggests that the pharmacological action of Panax quinquefolium L. is, at least partially, due to NO release. Our data demonstrate that American ginseng may play a therapeutic role in facilitating the hemodynamic balance of vascular endothelial cells.

scholarly journals In Vitro Vascular-Protective Effects of a Tilapia By-Product Oligopeptide on Angiotensin II-Induced Hypertensive Endothelial Injury in HUVEC by Nrf2/NF-κB Pathways

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 431 ◽  
Author(s):  
Jiali Chen ◽  
Fang Gong ◽  
Mei-Fang Chen ◽  
Chengyong Li ◽  
Pengzhi Hong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Umbilical Vein ◽  
Endothelial Injury ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Ang Ii

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.

Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway

2007 ◽  
Vol 292 (2) ◽  
pp. H893-H903 ◽  
Author(s):  
Galina N. Antonova ◽  
Connie M. Snead ◽  
Alexander S. Antonov ◽  
Christiana Dimitropoulou ◽  
Richard C. Venema ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Injury ◽  
Soluble Guanylate Cyclase ◽  
Heat Shock Protein 90 ◽  
Protective Effects ◽  
No Donor ◽  
Spermine Nonoate

Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)- N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 μM SNP, 10 μM spermine NONOate, or 100 μM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 μM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3- a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.

Hypoxia-induced pulmonary endothelin-1 expression is unaltered by nitric oxide

2002 ◽  
Vol 92 (3) ◽  
pp. 1152-1158 ◽  
Author(s):  
Scott Earley ◽  
Leif D. Nelin ◽  
Louis G. Chicoine ◽  
Benjimen R. Walker
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Promoter Activity ◽  
Umbilical Vein ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Exposure ◽  
Mrna Levels ◽  
Protective Effects ◽  
No Donor ◽  
Umbilical Vein Endothelial Cells

Nitric oxide (NO) attenuates hypoxia-induced endothelin (ET)-1 expression in cultured umbilical vein endothelial cells. We hypothesized that NO similarly attenuates hypoxia-induced increases in ET-1 expression in the lungs of intact animals and reasoned that potentially reduced ET-1 levels may contribute to the protective effects of NO against the development of pulmonary hypertension during chronic hypoxia. As expected, hypoxic exposure (24 h, 10% O2) increased rat lung ET-1 peptide and prepro-ET-1 mRNA levels. Contrary to our hypothesis, inhaled NO (iNO) did not attenuate hypoxia-induced increases in pulmonary ET-1 peptide or prepro-ET-1 mRNA levels. Because of this surprising finding, we also examined the effects of NO on hypoxia-induced increases in ET peptide levels in cultured cell experiments. Consistent with the results of iNO experiments, administration of the NO donor S-nitroso- N-acetyl-penicillamine to cultured bovine pulmonary endothelial cells did not attenuate increases in ET peptide levels resulting from hypoxic (24 h, 3% O2) exposure. In additional experiments, we examined the effects of NO on the activity of a cloned ET-1 promoter fragment containing a functional hypoxia inducible factor-1 binding site in reporter gene experiments. Whereas moderate hypoxia (24 h, 3% O2) had no effect on ET-1 promoter activity, activity was increased by severe hypoxic (24 h, 0.5% O2) exposure. ET-1 promoter activity after S-nitroso- N-acetyl-penicillamine administration during severe hypoxia was greater than that in normoxic controls, although activity was reduced compared with that in hypoxic controls. These findings suggest that hypoxia-induced pulmonary ET-1 expression is unaffected by NO.

scholarly journals C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis

2016 ◽  
Vol 231 (1) ◽  
pp. 97-108 ◽  
Author(s):  
Mahendra Prasad Bhatt ◽  
Yeon-Ju Lee ◽  
Se-Hui Jung ◽  
Yong Ho Kim ◽  
Jong Yun Hwang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Damage ◽  
Protective Effects ◽  
Diabetic Mice ◽  
C Peptide ◽  
Glucose Levels

C-peptide exerts protective effects against diabetic complications; however, its role in inhibiting hyperglycemic memory (HGM) has not been elucidated. We investigated the beneficial effect of C-peptide on HGM-induced vascular damage in vitro and in vivo using human umbilical vein endothelial cells and diabetic mice. HGM induced apoptosis by persistent generation of intracellular ROS and sustained formation of ONOO− and nitrotyrosine. These HGM-induced intracellular events were normalized by treatment with C-peptide, but not insulin, in endothelial cells. C-peptide also inhibited persistent upregulation of p53 and activation of mitochondrial adaptor p66shc after glucose normalization. Further, C-peptide replacement therapy prevented persistent generation of ROS and ONOO− in the aorta of diabetic mice whose glucose levels were normalized by the administration of insulin. C-peptide, but not insulin, also prevented HGM-induced endothelial apoptosis in the murine diabetic aorta. This study highlights a promising role for C-peptide in preventing HGM-induced intracellular events and diabetic vascular damage.

scholarly journals Dihydromyricetin alleviates endothelial inflammatory response through IRE1α/NF-κB signaling pathway in sepsis

2021 ◽  
Author(s):  
Xifeng Wang ◽  
Xiaomin Xu ◽  
Yu peng Yang ◽  
Xin Xin ◽  
Zekang Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Inflammatory Response ◽  
Er Stress ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Cecal Ligation ◽  
Protective Effects ◽  
Necrosis Factor Alpha

IntroductionThe high mortality of sepsis is closely related to disorder of coagulation induced by endothelial inflammatory response. Our aim is to investigate the protective effects of Dihydromyricetin (DHM) on endothelial cells in sepsis and the endoplasmic reticulum (ER) stress mechanism.Material and methodsIn vivo, we conducted an animal study for which fifty male Wistar rats were randomly and equally divided into five groups: sham group, cecal ligation and puncture (CLP) group and three CLP+ DHM (50, 100, 150 mg/kg) groups, the DHM was orally administered 2 h after CLP for 3 days (once per day). In vitro, human umbilical vein endothelial cells (HUVECs) were treated with DHM (50μmol) for 24 h after stimulation by lipopolysaccharide (LPS). In the inhibition groups, reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC, 3 mmol) and endoplasmic reticulum (ER) stress inhibitor (STF-083010, 10 μmol) were incubated prior to LPS.ResultsOur results indicated that DHM (150 mg/kg) alleviated the histopathological injury of endothelium, decreased the release of inflammatory cytokines and adhesion molecules such as interleukin-1β (IL-1β), interleukin-6 (IL-6) , tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) and endothelin-1 (ET-1), and inhibited the production of ROS production. In addition, we found that DHM ameliorated ER damage, significantly decreased the protein expressions of IRE1α/NF-κB signaling pathway.ConclusionsDHM treatment alleviated inflammatory response of endothelial cells in sepsis through the IRE1α/NF-κB signaling pathway triggered by oxidative stress. This study provided experimental rationale for the treatment of DHM on therapy of sepsis.

Abstract 152: IL-10 Inhibits Angiotensin II-induced Pathological Autophagy in Myocardium.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Suresh K Verma ◽  
Prasanna Krishnamurthy ◽  
Tatiana Abramova ◽  
Garikipati Srikanth ◽  
Mohsin Khan ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Fluorescent Protein ◽  
Heart Function ◽  
Cardiac Cells ◽  
Neonatal Rat ◽  
Autophagic Flux ◽  
Protective Effects ◽  
Ang Ii ◽  
Akt Inhibitor

Background: In heart, persistent pressure overload causes pathological autophagy leading to cardiac cell death and heart failure. The role IL-10, a pleiotropic anti-inflammatory cytokine, on pathological autophagy is largely unknown. Here we hypothesized that IL-10 inhibits stress-induced pathological autophagy and therefore attenuates cardiac cells death and improve heart function. Method and Results: Cardiac stress was induced in C57 BL/6 mice by Angiotensin II treatment (Ang II-1.2mg.kg b.wt/day for 28 days) using mini osmotic pumps. Ang II treatment markedly induced autophagy in mice as measured by electron microscopy (autophagosome numbers) and Western blotting (Becline1 and LC3II proteins expression). Interestingly, systemic recombinant mouse IL-10 administration markedly inhibited Ang II-induced autophagy. To further understand the mechanism of IL-10 protection, neonatal rat ventricular myocytes (NRCM) were transfected with monomeric Red Fluorescent Protein-Enhanced Green Fluorescent Protein (mRFP-EGFP) tandem fluorescent-tagged LC3 (tfLC3) adenovirus (to measure autophagic flux) and then treated with AngII (1μM) and/or IL-10 (20ng/mL), in vitro. Ang II treatment significantly increased the numbers of both yellow (merged EGFP and mRFP signals) and red puncta, indicating active formation of both autophagosomes and autolysosomes, however, this flux was strongly inhibited by IL-10. Furthermore, Ang II significantly increased the Beclin1 and LC3II proteins expression, which was markedly reduced by IL-10 as measured by Western blot analysis. In addition, Ang II-inhibited AKT signaling (anti-autophagic signaling component) was strongly enhanced by IL-10. Ang II-induced autophagic signaling was mimicked by AKT inhibitor, suggesting AKT as the downstream target of IL-10 effects. Conclusion: Inhibition of pathological autophagy is a novel mechanism for cardio-protective effects of IL-10.

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