Radix pseudostellariae of Danzhi Jiangtang capsule relieves oxidative stress of vascular endothelium in diabetic macroangiopathy

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

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Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection

AJP Cell Physiology ◽

10.1152/ajpcell.00386.2005 ◽

2006 ◽

Vol 290 (5) ◽

pp. C1399-C1410 ◽

Cited By ~ 112

Author(s):

Helena Parfenova ◽

Shyamali Basuroy ◽

Sujoy Bhattacharya ◽

Dilyara Tcheranova ◽

Yan Qu ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Endothelial Cells ◽

Vascular Endothelium ◽

Vascular Endothelial Cells ◽

Glutamate Toxicity ◽

Vascular Endothelial ◽

Oxygen Species ◽

Apoptotic Effects ◽

Cerebral Vascular

In cerebral circulation, epileptic seizures associated with excessive release of the excitatory neurotransmitter glutamate cause endothelial injury. Heme oxygenase (HO), which metabolizes heme to a vasodilator, carbon monoxide (CO), and antioxidants, biliverdin/bilirubin, is highly expressed in cerebral microvessels as a constitutive isoform, HO-2, whereas the inducible form, HO-1, is not detectable. Using cerebral vascular endothelial cells from newborn pigs and HO-2-knockout mice, we addressed the hypotheses that 1) glutamate induces oxidative stress-related endothelial death by apoptosis, and 2) HO-1 and HO-2 are protective against glutamate cytotoxicity. In cerebral endothelial cells, glutamate (0.1–2.0 mM) increased formation of reactive oxygen species, including superoxide radicals, and induced major keystone events of apoptosis, such as NF-κB nuclear translocation, caspase-3 activation, DNA fragmentation, and cell detachment. Glutamate-induced apoptosis was greatly exacerbated in HO-2 gene-deleted murine cerebrovascular endothelial cells and in porcine cells with pharmacologically inhibited HO-2 activity. Glutamate toxicity was prevented by superoxide dismutase, suggesting apoptotic changes are oxidative stress related. When HO-1 was pharmacologically upregulated by cobalt protoporphyrin, apoptotic effects of glutamate in cerebral endothelial cells were completely prevented. Glutamate-induced reactive oxygen species production and apoptosis were blocked by a CO-releasing compound, CORM-A1 (50 μM), and by bilirubin (1 μM), consistent with the antioxidant and cytoprotective roles of the end products of HO activity. We conclude that both HO-1 and HO-2 have anti-apoptotic effects against oxidative stress-related glutamate toxicity in cerebral vascular endothelium. Although HO-1, when induced, provides powerful protection, HO-2 is an essential endogenous anti-apoptotic factor against glutamate toxicity in the cerebral vascular endothelium.

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Atorvastatin improves function of vascular endothelium by decreasing oxidative stress

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.617.18 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Jian Wang ◽

Xiaochen Ru ◽

Lingbo Qian ◽

Yeqiang Tu ◽

Qiang Xia

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium

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Protection of the vascular endothelium in experimental situations

Interdisciplinary Toxicology ◽

10.2478/v10102-011-0005-y ◽

2011 ◽

Vol 4 (1) ◽

pp. 20-26 ◽

Cited By ~ 16

Author(s):

Ružena Sotníková ◽

Jana Nedelčevová ◽

Jana Navarová ◽

Viera Nosáľová ◽

Katarína Drábiková ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium ◽

Vascular Dysfunction ◽

Antioxidant Properties ◽

Pharmacological Intervention ◽

Ros Production ◽

Nitric Oxide Radical ◽

Endothelium Dependent Relaxation

Protection of the vascular endothelium in experimental situationsOne of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 foundin vitrowere partly confirmedin vivo.Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effectin vivo.

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Overexpression of the Superoxide Anion and NADPH Oxidase Isoforms 1 and 4 (NOX1 and NOX4) in Allergic Nasal Mucosa

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2009.23.3340 ◽

2009 ◽

Vol 23 (4) ◽

pp. 370-376 ◽

Cited By ~ 12

Author(s):

Joon Hwan Moon ◽

Tae Hoon Kim ◽

Heung Man Lee ◽

Seung Hoon Lee ◽

Whan Choe ◽

...

Keyword(s):

Oxidative Stress ◽

Allergic Rhinitis ◽

Nadph Oxidase ◽

Nasal Mucosa ◽

Vascular Endothelium ◽

Superoxide Anion ◽

Nasal Polyps ◽

Inflammatory Cells ◽

Submucosal Glands ◽

Cellular Source

Background The purpose of this study was to investigate the expression and distribution of superoxide anion, NADPH oxidase (NOX)1, and NOX4 in healthy, allergic nasal mucosa and nasal polyps to evaluate the possible influence of oxidative stress on the development of allergic rhinitis and nasal polyps. Methods The expression and distribution of superoxide anion, NOX1 and NOX4 were evaluated in healthy and allergic nasal mucosa and nasal polyps, using dihydroethidium fluorescence, semiquantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blot. Results NOX1 and NOX4 were localized mainly in the epithelial layer, submucosal glands, vascular endothelium, and inflammatory cells in healthy and allergic nasal mucosa and nasal polyps. The cellular source that generated superoxide anion is also localized in the epithelial cells, submucosal glands, vascular endothelium, and inflammatory cells, demonstrating the similar sites of expression of NOX1 and NOX4 in healthy and allergic nasal mucosa and nasal polyps. NOX1 and NOX4 mRNA and proteins and superoxide anions had increased levels of expression in allergic nasal mucosa and nasal polyps compared with healthy nasal mucosa. Conclusions These results indicate that NOX1 and NOX4 may play an important role in reactive oxygen species production, contributing to the oxidative stress in allergic rhinitis and nasal polyp tissues.

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Nanotargeting Dementia Etiology: Aiming Drug Nanocarriers Toward Receptors for Vascular Endothelium, Serum Amyloid A, Inflammasomes, and Oxidative Stress

Nano Progress ◽

10.36686/ariviyal.np.2020.02.03.011 ◽

2020 ◽

Vol 2 (3) ◽

Author(s):

Joseph S. D'Arrigo

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium ◽

Serum Amyloid A ◽

Serum Amyloid ◽

Amyloid A ◽

Drug Nanocarriers ◽

And Oxidative Stress

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Abstract 14993: Dysfunctional Extracellular Microvesicles in Andean Highlanders With Excessive Erythrocytosis

Circulation ◽

10.1161/circ.142.suppl_3.14993 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Madden Brewster ◽

Anthony R Bain ◽

Vinicius P Garcia ◽

Hannah K Fandl ◽

Rachel Stone ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium ◽

Cardiovascular Health ◽

Vascular Dysfunction ◽

Umbilical Vein ◽

No Production ◽

Intracellular Expression ◽

Cerro De Pasco ◽

Umbilical Vein Endothelial Cells ◽

Cell Expression

Background: Chronic mountain sickness, a maladaptation to high altitude (>2,500 m) characterized by excessive erythrocytosis (EE) and often severe hypoxemia, is prevalent in Andean highlanders. EE increases the risk of cardiovascular events and contributes to vascular dysfunction. Circulating extracellular microvesicles (MVs) are key mediators of cardiovascular health and disease through their interaction with the vascular endothelium. The experimental aim of this study was to determine the effects of MVs isolated from adults with EE on endothelial cell inflammation, oxidative stress, apoptosis and nitric oxide (NO) production. Methods: Twenty-six male residents of Cerro de Pasco, Peru (4,340 m) were studied: 12 highlanders without EE (healthy; age: 40±4 yr; BMI: 26.4±1.7; Hb: 17.4±0.5 g/dL, SpO 2 : 86.9±1.0%) and 14 highlanders with EE (EE: 43±4 yr; 26.2±0.9; 24.4±0.4 g/dL; 79.7±1.6%). MVs were isolated from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with MVs from either healthy or EE men. Results: MVs from highlanders with EE induced significantly higher release of interleukin (IL)-6 (89.8±2.7 vs 77.1±1.9 pg/mL) and IL-8 (62.0±2.7 vs 53.3±2.2 pg/mL) compared with MVs from healthy highlanders. Although intracellular expression of total NF-κB p65 (65.3±6.0 vs 74.9±7.8.9 AU) was not significantly affected, MVs from EE men resulted in ~25% higher (P<0.05) expression of p-NF-κB p65 (Ser536; active NF-κB) (173.6±14.3 vs 132.8±12.2 AU). Additionally, cell expression of the anti-inflammatory miR-146a and miR-181b were significantly suppressed by EE MVs. Cell oxidative stress and apoptotic susceptibility were not significantly affected by MVs from EE men. However, eNOS activation (231.3±15.5 vs 286.6±23.0 AU) and NO production (8.3±0.6 vs 10.7±0.7 μM/L) were significantly lower in cells treated with MVs from EE vs healthy men. Conclusion: Increased inflammation and decreased eNOS activity and NO production renders the vascular endothelium highly susceptible to atherosclerosis and thrombosis. Andean highlanders with EE exhibit dysfunctional circulating extracellular MVs that induce a proatherogenic endothelial phenotype contributing to their increased cardiovascular risk.

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Oxidative injury of coronary venular endothelial cells depletes intracellular glutathione and induces HSP 70 mRNA

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.4.h1651 ◽

1995 ◽

Vol 268 (4) ◽

pp. H1651-H1658 ◽

Cited By ~ 4

Author(s):

M. M. Aucoin ◽

R. Barhoumi ◽

D. T. Kochevar ◽

H. J. Granger ◽

R. C. Burghardt

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Vascular Endothelium ◽

Heat Shock Protein 70 ◽

Ischemia Reperfusion ◽

Oxygen Species ◽

Hsp 70 ◽

Intracellular Glutathione ◽

Myocardial Ischemia Reperfusion

Vascular endothelium is one of the first tissues exposed to reactive oxygen species produced during myocardial ischemia-reperfusion. Bovine coronary venular endothelial cells (CVEC) were evaluated for intracellular glutathione (GSH) levels and heat shock protein 70 (HSP 70) mRNA and protein during in vitro oxidative stress. CVEC were incubated with 0.01875 U/ml xanthine oxidase (XO) and 0.5 mM hypoxanthine (HX) for 30 min and then allowed to recover for 0, 1, 2, or 3 h. Relative GSH levels were determined by evaluation of monochlorobimane fluorescence. GSH fluorescence was significantly lower in CVEC treated with XO+HX for 30 min than in controls. GSH fluorescence was also decreased in heat-shocked CVEC. After oxidative stress, GSH levels were higher than in controls at 1 h, but by 2 or 3 h after treatment, GSH fluorescence fell below control values. HSP 70 mRNA was induced in CVEC by a 30-min treatment with XO+HX exposure. These data suggest that CVEC respond to oxidative stress by reducing intracellular GSH levels and inducing HSP 70 mRNA, although significant increases in HSP 70 protein were not detected at the time points tested.

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Aspirin Eugenol Ester Protects Vascular Endothelium From Oxidative Injury by the Apoptosis Signal Regulating Kinase-1 Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.588755 ◽

2020 ◽

Vol 11 ◽

Author(s):

Mei-Zhou Huang ◽

Zhen-Dong Zhang ◽

Ya-Jun Yang ◽

Xi-Wang Liu ◽

Zhe Qin ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Endothelium ◽

Cell Apoptosis ◽

Oxidative Injury ◽

Vital Role ◽

Stress Effect ◽

Antioxidative Stress ◽

Aspirin Eugenol Ester

Aspirin eugenol ester (AEE) is a new potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress activity. The pharmacological activities of AEE are partly dependent on its regulation of cell apoptosis. However, it is still unclear how AEE inhibits cell apoptosis on the basis of its antioxidative stress effect. This study aimed to reveal the vascular antioxidative mechanism of AEE in response to H2O2-induced oxidative stress in HUVECs and paraquat-induced oxidative stress in rats. In the different intervention groups of HUVECs and rats, the expression of ASK1, ERK1/2, SAPK/JNK, and p38 and the phosphorylation levels of ERK1/2, SAPK/JNK, and p38 were measured. The effects of ASK1 and ERK1/2 on the anti-apoptotic activity of AEE in the oxidative stress model were probed using the corresponding inhibitors ASK1 and ERK1/2. The results showed that in the HUVECs, 200 μM H2O2 treatment significantly increased the phosphorylation of SAPK/JNK and the level of ASK1 but decreased the phosphorylation of ERK1/2, while in the HUVECs pretreated with AEE, the H2O2-induced changes were significantly ameliorated. The findings were observed in vitro and in vivo. Moreover, inhibition of ASK1 and ERK1/2 showed that ASK1 plays a vital role in the protective effect of AEE on H2O2-induced apoptosis. All findings suggested that AEE protects the vascular endothelium from oxidative injury by mediating the ASK1 pathway.

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