Editorial: Oxidative Stress Revisited—Major Role in Vascular Diseases, Volume II

Organismal aging represents an independent risk factor underlying many vascular diseases, including systemic and pulmonary hypertension, and atherosclerosis. While the mechanisms driving aging are largely elusive, a steady persistent increase in tissue oxidative stress has been associated with senescence. Previously we showed TSP1 elicits NADPH oxidase (Nox)-dependent vascular smooth muscle cell oxidative stress. However mechanisms by which TSP1 affects endothelial redox biology are unknown. Here, we tested the hypothesis that TSP1 induces endothelial oxidative stress-linked senescence in aging. Using rapid autopsy disease-free human pulmonary (PA) artery, we identified a significant positive correlation between age, protein levels of TSP1, Nox1 and the cell-cycle repressor p21cip (p<0.05). Age also positively associated with increased Amplex Red-detected PA hydrogen peroxide levels (p<0.05). Moreover, treatment of human PA endothelial cells (HPAEC) with TSP1 (2.2nM; 24h) increased expression (~1.9 fold; p<0.05) and activation of Nox1 (~1.7 fold; p<0.05) compared to control, as assessed by Western blot and SOD-inhibitable cytochrome c reduction. Western blotting and immunofluorescence showed a TSP1-mediated increase in p53 activation, indicative of the DNA damage response. Moreover, TSP1 significantly increased HPAEC senescence in a p53/p21cip/Rb-dependent manner, as assessed by immunofluorescent detection of subcellular localization and senescence-associated β-galactosidase staining. To explore this pathway in vivo, middle-aged (8-10 month) wild-type and TSP1-null mice were utilized. In the TSP1-null, reduced lung senescence, oxidative stress, Nox1 levels and p21cip expression were observed compared to wild-type supporting findings in human samples and cell experiments. Finally, prophylactic treatment with specific Nox1 inhibitor NoxA1ds (10μM) attenuated TSP1-induced HPAEC ROS, p53 activation, p21cip expression and senescence. Taken together, our results provide molecular insight into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence, with implications for molecular control of the aging process.

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Oxidative Stress and Vascular Diseases: Effect of Physical Exercise

Free Radicals, Antioxidants and Diseases ◽

10.5772/intechopen.76576 ◽

2018 ◽

Author(s):

Aline de Freitas Brito ◽

Caio Victor Coutinho de Oliveira ◽

Glêbia Alexa Cardoso ◽

Joana Marcela Sales de Lucena ◽

Jordanna di Paula dos Santos Sousa ◽

...

Keyword(s):

Oxidative Stress ◽

Physical Exercise ◽

Vascular Diseases

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Soluble guanylyl cyclase activation by HMR-1766 (ataciguat) in cells exposed to oxidative stress

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.51.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. H1763-H1771 ◽

Cited By ~ 28

Author(s):

Zongmin Zhou ◽

Anastasia Pyriochou ◽

Anastasia Kotanidou ◽

Georgios Dalkas ◽

Martin van Eickels ◽

...

Keyword(s):

Oxidative Stress ◽

Vascular Tone ◽

Soluble Guanylyl Cyclase ◽

Vascular Diseases ◽

Wild Type ◽

Cross Tolerance ◽

Wild Type Enzyme ◽

Tolerance Development ◽

Cgmp Formation ◽

In Cells

Many vascular diseases are characterized by increased levels of ROS that destroy the biological activity of nitric oxide and limit cGMP formation. In the present study, we investigated the cGMP-forming ability of HMR-1766 in cells exposed to oxidative stress. Pretreatment of smooth muscle cells with H2O2reduced cGMP production stimulated by sodium nitroprusside (SNP) or BAY 41-2272. However, pretreatment with H2O2significantly increased HMR-1766 responses. Similar results were obtained with SIN-1, menadione, and rotenone. In addition, HMR-1766 was more effective in stimulating heme-free sGC compared with the wild-type enzyme. Interestingly, in cells expressing heme-free sGC, H2O2inhibited instead of potentiated HMR-1766 responses, suggesting that the ROS-induced enhancement of cGMP formation was heme dependent. Moreover, using truncated forms of sGC, we observed that the NH2-terminus of the β1-subunit is required for the action of HMR-1766. Finally, to study tolerance development to HMR-1766, cells were pretreated with this sGC activator and reexposed to HMR-1766 or SNP. Results from these experiments demonstrated lack of tolerance development to HMR-1766 as well as lack of cross-tolerance with SNP. We conclude that HMR-1766 is an improved sGC activator as it has the ability to activate oxidized/heme-free sGC and is resistant to the development of tolerance; these observations make HMR-1766 a promising agent for treating diseases associated with increased vascular tone combined with enhanced ROS production.

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α-Lipoic acid protects HAECs from high glucose-induced apoptosis via decreased oxidative stress, ER stress and mitochondrial injury

RSC Advances ◽

10.1039/c5ra09460g ◽

2015 ◽

Vol 5 (87) ◽

pp. 70726-70736

Author(s):

Wenshuang Li ◽

Changyuan Wang ◽

Jinyong Peng ◽

Jing Liang ◽

Yue Jin ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Er Stress ◽

Lipoic Acid ◽

High Glucose ◽

Vascular Diseases ◽

Mitochondrial Injury ◽

Wide Range ◽

Induced Apoptosis

α-Lipoic acid (LA) has a wide range of benefits in treating diabetes mellitus (DM) and DM vascular diseases, however, the specific mechanisms are not clearly understood.

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The influence of oxidized fibrinogen on apoptosis of endothelial cells

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20115702210 ◽

2011 ◽

Vol 57 (2) ◽

pp. 210-218 ◽

Cited By ~ 1

Author(s):

A.V. Aseychev ◽

O.A. Azizova ◽

O.N. Scheglovitova ◽

N.N. Sklyankina ◽

G.G. Borisenko

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Cell Death ◽

Critical Role ◽

Vascular Diseases ◽

Oxidative Modification ◽

Cell Protection ◽

Oxidized Fibrinogen ◽

Atherosclerosis Development ◽

Cardio Vascular

Oxidative stress plays an important role in cardio-vascular diseases and atherosclerosis. Fibrinogen (FB), plasma coagulation protein, is a risk factor of atherosclerosis. Importantly, it can be readily oxidized during oxidative stress and in pathological conditions. FB can promote angiogenesis by supporting migration and proliferation of endothelial cells. On the other hand, recent reports demonstrated cytotoxicity of oxidized fibrinogen (oxFB). Endothelial dysfunction plays a critical role in the atherosclerosis development, therefore it is important to understand the effect of oxFB on human endothelial cells (hEC), and the mechanism of the cell death. Here, we studied influence of oxFB on hEC during 24 h incubation in two conditions: (1) at low serum level (0.1%) and in the absence of growth factors ("starvation"); (2) in full medium (5% FBS) with growth factor supplement. Apoptosis was evaluated using analysis of nuclear morphology, phosphatidylserine externalization on hEC surface and caspase-3 activation. In starvation, we observed significant cell death via apoptosis. FB prevented starvation-induced cell death and caspase activation. Caspase activity in the presence of oxFB was 1.5 times higher as compared to FB, yet oxFB demonstrated significant cell protection during stress. Similarly, in optimal cultivation conditions FB decreased the rate of apoptosis by three times, while oxFB supported cell viability to the lesser extent. Thus, FB can protect hEC in stress conditions (in starvation); oxidative modification of FB diminishes its antiapoptotic properties.

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Therapeutic Potential of Heme Oxygenase-1 in Aneurysmal Diseases

Antioxidants ◽

10.3390/antiox9111150 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1150

Author(s):

Wei-Cheng Jiang ◽

Chen-Mei Chen ◽

Candra D. Hamdin ◽

Alexander N. Orekhov ◽

Igor A. Sobenin ◽

...

Keyword(s):

Oxidative Stress ◽

Heme Oxygenase ◽

Therapeutic Potential ◽

Tissue Injury ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Vascular Diseases ◽

High Rate ◽

Heme Oxygenase 1 ◽

High Morbidity ◽

Attractive Option

Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH.

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Effects of Rosiglitazone with Insulin Combination Therapy on Oxidative Stress and Lipid Profile in Left Ventricular Muscles of Diabetic Rats

Experimental Diabetes Research ◽

10.1155/2012/905683 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Servet Kavak ◽

Lokman Ayaz ◽

Mustafa Emre

Keyword(s):

Oxidative Stress ◽

Blood Glucose ◽

Lipid Profile ◽

Nitrosative Stress ◽

Vascular Diseases ◽

Diabetic Rats ◽

Left Ventricular ◽

Control Group ◽

Group B ◽

Group D

Purpose. In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation.Methods and Materials. Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mgkg−1), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured.Result. Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D(P<0.05).Conclusion. Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.

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Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.3.h1364 ◽

2001 ◽

Vol 281 (3) ◽

pp. H1364-H1371 ◽

Cited By ~ 23

Author(s):

Takatoshi Saito ◽

Hiroshi Itoh ◽

Tae-Hwa Chun ◽

Yasutomo Fukunaga ◽

Jun Yamashita ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Mrna Expression ◽

Vascular Diseases ◽

Transcriptional Level ◽

Dependent Manner ◽

Camp Pathway ◽

Intracellular Ca ◽

Dose Dependent Fashion ◽

Dose Dependent

To elucidate the significance of oxidative stress in the modulation of endothelial functions, we examined the effects of H2O2 on the expression of two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin (Am), and their interaction. H2O2 dose dependently suppressed ET secretion and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose-dependent manner. Catalase, a H2O2 reductase, and dl-α-tocopherol (vitamin E) significantly inhibited H2O2-induced suppression of ET secretion. Downregulation of ET-1 mRNA under oxidative stress was regulated at the transcriptional level. In contrast, H2O2increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production. Am, as well as 8-bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion. Furthermore, an anti-Am monoclonal antibody that we developed abolished H2O2-induced suppression of ET secretion at 6–24 h after the addition of H2O2. H2O2 increased the intracellular Ca2+ concentration ([Ca2+]i). Moreover, treatment with ionomycin, a Ca2+ ionophore, and thapsigargin, an inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose dependently for 3 h. These results suggest that the production of ET was decreased via activation of the Am-cAMP pathway and by the elevation of [Ca2+]i under oxidative stress. These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases.

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Carotenoids Inhibit Fructose-Induced Inflammatory Response in Human Endothelial Cells and Monocytes

Mediators of Inflammation ◽

10.1155/2020/5373562 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Ping Lin ◽

Qian Ren ◽

Qin Wang ◽

Jiali Wu

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Inflammatory Response ◽

Umbilical Vein ◽

Vascular Diseases ◽

Monocyte Adhesion ◽

Endothelial Adhesion Molecules ◽

Umbilical Vein Endothelial Cells ◽

Excessive Inflammatory Response ◽

Intracellular Oxidative Stress

Objective. This research is aimed at determining the vascular health characteristics of carotenoids by evaluating their effect on excessive inflammatory response in endothelial and monocyte cells, the main factors of atherosclerosis. Methods. Human umbilical vein endothelial cells (HUVECs) or U937 monocytes were treated with escalating concentrations (0.1, 0.5, and 1 μM) of five most common carotenoids in human plasma, i.e., α-carotene, β-carotene, β-cryptoxanthin, lutein, and lycopene prior to stimulation with 2 mM fructose. We examined the monocyte adhesion to endothelial cells (ECs) and relevant endothelial adhesion molecules. Chemokine and proinflammatory cytokine production as well as intracellular oxidative stress were also assessed in fructose-stimulated ECs and monocytes. Results. Carotenoids repressed monocyte adhesion to fructose-stimulated ECs dose dependently via decreasing primarily the expression of endothelial VCAM-1. In ECs and monocytes, three carotenoids, i.e., β-cryptoxanthin, lutein, and lycopene, suppressed the fructose-induced expression of chemokines MCP-1, M-CSF, and CXCL-10 and inflammatory cytokines TNF-α and IL-1β, with CXCL-10 being the most repressed inflammatory mediator. β-Cryptoxanthin, lutein, and lycopene dramatically downregulated the fructose-induced CXCL-10 expression in vascular cells. The reduction in the inflammatory response was associated with a slight but significant decrease of intracellular oxidative stress. Conclusions. Our results show that carotenoids have a variety of anti-inflammatory and antiatherosclerosis activities, which can help prevent or reduce fructose-induced inflammatory vascular diseases.

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