scholarly journals Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Audrey Dooley ◽  
K. Richard Bruckdorfer ◽  
David J. Abraham
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Systemic Sclerosis ◽  
Free Radical ◽  
Animal Models ◽  
Connective Tissue ◽  
Vascular Dysfunction ◽  
Oxidant Stress ◽  
Unknown Aetiology ◽  
Protective System

Systemic sclerosis (scleroderma: SSc) is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO), a key mediator of oxidative stress, can profoundly influence the early microvasculopathy, and possibly the ensuing fibrogenic response. Animal models and human studies have also identified dietary antioxidants, such as epigallocatechin-3-gallate (EGCG), to function as a protective system against oxidative stress and fibrosis. Hence, targeting EGCG may prove a possible candidate for therapeutic treatment aimed at reducing both oxidant stress and the fibrotic effects associated with SSc.

Autoimmune atrophic gastritis in systemic sclerosis

2021 ◽  
Vol 14 (8) ◽  
pp. e242851
Author(s):  
Deepti Avasthi ◽  
Jean Thomas ◽  
Leela Krishna Vamsee Miriyala ◽  
Salil Avasthi
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Literature Review ◽  
Atrophic Gastritis ◽  
Vascular Dysfunction ◽  
Connective Tissue Disorder ◽  
Gastric Antral Vascular Ectasia ◽  
Innate And Adaptive Immunity ◽  
Common Presentation ◽  
Autoimmune Atrophic Gastritis

Systemic sclerosis (SSc) is a rare connective tissue disorder with a complex pathogenesis involving vascular dysfunction, small vessel proliferation as well as alterations of innate and adaptive immunity. Gastrointestinal (GI) involvement in SSc is almost universal and affects nearly 90% of the patients. Of all the GI manifestations, 30%–75% are oesophageal abnormalities, including gastro-oesophageal reflux disease, reflux oesophagitis and Barret’s oesophagus. The incidence of gastric manifestations is about 22% with a common presentation of gastric antral vascular ectasia (GAVE). However, autoimmune atrophic gastritis (AIG) is not a known manifestation of SSc. Our case has a unique presentation of the coexistence of GAVE and AIG. We have conducted a thorough literature review to study a possible association of AIG and SSc and understand the pathology of SSc.

scholarly journals Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2

2020 ◽  
Vol 33 (7) ◽  
pp. 610-619 ◽  
Author(s):  
Peijian Wang ◽  
Yi Yang ◽  
Dan Wang ◽  
Qiyuan Yang ◽  
Jindong Wan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Related Factor ◽  
Diabetic Mice ◽  
Quinone Oxidoreductase ◽  
Nrf2 Signaling Pathway

Abstract BACKGROUND Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.

Free radical biology and medicine: it's a gas, man!

2006 ◽  
Vol 291 (3) ◽  
pp. R491-R511 ◽  
Author(s):  
William A. Pryor ◽  
Kendall N. Houk ◽  
Christopher S. Foote ◽  
Jon M. Fukuto ◽  
Louis J. Ignarro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Free Radical ◽  
Cell Signaling ◽  
Adaptive Responses ◽  
Adaptive Mechanisms ◽  
Low Levels ◽  
Very High ◽  
Ozone Reactions

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O2 toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen (3O2), and the more energetic, reactive singlet oxygen (1O2). Nitric oxide (·NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, ·NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (CO2), and hydrogen sulfide (H2S). Like ·NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO3·−) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish “cross talk” between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.

scholarly journals Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Samira Tajbakhsh ◽  
Kamelya Aliakbari ◽  
Damian J. Hussey ◽  
Karen M. Lower ◽  
Anthony J. Donato ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Sirtuin 1 ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Clinical Complications

Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D) and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1per seare not sufficient to prematurely shorten vascular telomeres.

Oxidative Stress and Hypertension

2021 ◽  
Vol 128 (7) ◽  
pp. 993-1020
Author(s):  
Kathy K. Griendling ◽  
Livia L. Camargo ◽  
Francisco J. Rios ◽  
Rhéure Alves-Lopes ◽  
Augusto C. Montezano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Animal Models ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Reactive Oxygen ◽  
Antioxidant Systems ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Organ Systems

A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modify complex signaling pathways to promote hypertension has expanded significantly. In this review, we summarize recent advances in delineating the primary and secondary sources of reactive oxygen species (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, endoplasmic reticulum, and mitochondria), the posttranslational oxidative modifications they induce on protein targets important for redox signaling, their interplay with endogenous antioxidant systems, and the role of inflammasome activation and endoplasmic reticular stress in the development of hypertension. We highlight how oxidative stress in different organ systems contributes to hypertension, describe new animal models that have clarified the importance of specific proteins, and discuss clinical studies that shed light on how these processes and pathways are altered in human hypertension. Finally, we focus on the promise of redox proteomics and systems biology to help us fully understand the relationship between ROS and hypertension and their potential for designing and evaluating novel antihypertensive therapies.

Abstract 15326: Inactivation of Mitochondrial Deacetylase Sirt3 Induces Oxidative Stress, Promotes Vascular Hypertrophy, Increases Aortic Dissections, Exacerbates Hypertension and Mortality

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anna Dikalova ◽  
Sergey Gutor ◽  
Vasiliy Polosukhin ◽  
Sergey Dikalov
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Aortic Dissection ◽  
Vascular Dysfunction ◽  
Vascular Hypertrophy ◽  
Abdominal Aortic ◽  
Aortic Dissections

Introduction: Vascular dysfunction plays a key role in hypertension and cardiovascular disease, which causes one-third of deaths worldwide. Mitochondrial dysfunction contributes to these conditions; however, specific mechanisms are not clear. We showed inactivation of mitochondrial deacetylase Sirt3 in arterioles from patients with essential hypertension associated with superoxide dismutase inactivation, vascular inflammation and oxidative stress. Hypothesis: We hypothesized that the loss of vascular Sirt3 induces oxidative stress, promotes vascular dysfunction and hypertension. Methods: To test this hypothesis, we developed tamoxifen-inducible smooth muscle specific Sirt3 knockout mice (SmcSirt3KO) by crossing the Sirt3flox/flox mice with mice carrying a gene for inducible Cre in the vascular smooth muscle cells. Results and Discussion: Hypertension was modestly increased but considerably increased mortality in angiotensin II-infused SmcSirt3KO mice (35% vs 5% in WT) which was associated with higher rate of aortic dissections (50% vs 10% in WT). The basal superoxide and nitric oxide levels were not affected in SmcSirt3KO mice, however, angiotensin II infusion significantly increased superoxide and nitric oxide inactivation in SmcSirt3KO mice compared with wild-type mice supporting the pathological role of smooth muscle Sirt3 impairment. Post-mortem analysis showed high frequency of abdominal aortic aneurysms in angiotensin II-infused SmcSirt3KO mice suggesting that adverse vascular remodeling contributed to high mortality in these mice. To gain further insight into vascular pathology we performed histological examination using Verhoeff-van Gieson staining. Angiotensin II-infused SmcSirt3KO mice had 5-time higher abdominal aortic dissections rate, increased vascular hypertrophy, and disrupted elastic lamellae. Conclusion: Aortic dissection is a catastrophic disease with high mortality and morbidity characterized by fragmentation of elastin and smooth muscle cell dysfunction. Our data suggest that Sirt3 impairment can contribute to vascular hypertrophy, aortic dissection, end-organ-damage and mortality. It is conceivable that targeting Sirt3 may have therapeutic potential in cardiovascular disease.

scholarly journals Nitric Oxide, Oxidative Stress, andp66ShcInterplay in Diabetic Endothelial Dysfunction

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Alessandra Magenta ◽  
Simona Greco ◽  
Maurizio C. Capogrossi ◽  
Carlo Gaetano ◽  
Fabio Martelli
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Complex Interplay ◽  
Cell Dysfunction ◽  
Intracellular Ros ◽  
No Bioavailability

Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production,p66Shcprotein.

scholarly journals Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis

2009 ◽  
Vol 297 (2) ◽  
pp. L209-L216 ◽  
Author(s):  
Gin C. Chuang ◽  
Zhen Yang ◽  
David G. Westbrook ◽  
Melissa Pompilius ◽  
Carol A. Ballinger ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Hospital Admissions ◽  
Vascular Dysfunction ◽  
Oxidant Stress ◽  
Atherosclerotic Lesion ◽  
The United States ◽  
Mitochondrial Damage ◽  
Ozone Exposure ◽  
Environmental Toxicants

More than 100 million people in the United States live in areas that exceed current ozone air quality standards. In addition to its known pulmonary effects, environmental ozone exposures have been associated with increased hospital admissions related to cardiovascular events, but to date, no studies have elucidated the potential molecular mechanisms that may account for exposure-related vascular impacts. Because of the known pulmonary redox and immune biology stemming from ozone exposure, we hypothesized that ozone inhalation would initiate oxidant stress, mitochondrial damage, and dysfunction within the vasculature. Accordingly, these factors were quantified in mice consequent to a cyclic, intermittent pattern of ozone or filtered air control exposure. Ozone significantly modulated vascular tone regulation and increased oxidant stress and mitochondrial DNA damage (mtDNA), which was accompanied by significantly decreased vascular endothelial nitric oxide synthase protein and indices of nitric oxide production. To examine influences on atherosclerotic lesion formation, apoE−/− mice were exposed as above, and aortic plaques were quantified. Exposure resulted in significantly increased atherogenesis compared with filtered air controls. Vascular mitochondrial damage was additionally quantified in ozone- and filtered air-exposed infant macaque monkeys. These studies revealed that ozone increased vascular mtDNA damage in nonhuman primates in a fashion consistent with known atherosclerotic lesion susceptibility in humans. Consequently, inhaled ozone, in the absence of other environmental toxicants, promotes increased vascular dysfunction, oxidative stress, mitochondrial damage, and atherogenesis.

Sign in / Sign up

Export Citation Format

Share Document