scholarly journals An Insight into Giant Cell Arteritis Pathogenesis: Evidence for Oxidative Stress and SIRT1 Downregulation

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 885
Author(s):  
Alessandro Ianni ◽  
Poonam Kumari ◽  
Shahriar Tarighi ◽  
Flavia Rita Argento ◽  
Eleonora Fini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Vascular Complications ◽  
The Elderly ◽  
Ros Production ◽  
Healthy Controls ◽  
Sirt1 Expression ◽  
Systemic Oxidative Stress ◽  
Myocardial Infraction

Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase (p < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression (p < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.

Polymyalgia Rheumatica - a Disease of the Elderly

2018 ◽  
Vol 69 (1) ◽  
pp. 152-154
Author(s):  
Vasilica Cristescu ◽  
Aurelia Romila ◽  
Luana Andreea Macovei
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Polymyalgia Rheumatica ◽  
Temporal Arteritis ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
The Elderly ◽  
Clinical Aspects ◽  
Immune Disorder ◽  
Markers Of Inflammation

Polymyalgia rheumatica is a disease that occurs mostly in the elderly and is rarely seen in patients less than 50 years of age. Polymyalgia rheumatica is a vasculitis, which manifests itself as an inflammatory disease of the vascular wall that can affect any type of blood vessel, regardless of its size. It has been considered a form of giant cell arteritis, involving primarily large and medium arteries and to a lesser extent the arterioles. Clinical manifestations are caused by the generic pathogenic process and depend on the characteristics of the damaged organ. PMR is a senescence-related immune disorder. It has been defined as a stand-alone condition and a syndrome referred to as rheumatic polyarteritis with manifestations of giant cell arteritis (especially in cases of Horton�s disease and temporal arteritis) which are commonly associated with polymyalgia. The clinical presentation is clearly dominated by the painful girdle syndrome, with a feeling of general discomfort. Polymyalgia and temporal arteritis may coexist or be consecutive to each other in the same patient, as in most of our patients. The present study describes 3 cases of polymyalgia rheumatica, admitted to the Clinic of Rheumatology of Sf. Apostol Andrei Hospital, Galati. The cases were compared with the literature. Two clinical aspects (polymyalgia rheumatica and/or Horton�s disease) and the relationship between them were also considered. Polymyalgia rheumatica is currently thought to have a multifactorial etiology, in which the following factors play a role: genetic factors or hereditary predisposition (some individuals are more prone to this disease), immune factors and viral infections (triggers of the disease). Other risk factors of polymyalgia rheumatica include age over 50 years and the association with giant cell arteritis. The characteristic feature of the disease is girdle pain, with intense stiffness of at least one hour�s duration. Markers of inflammation, erythrocyte sedimentation rate and C-reactive protein are almost always increased at the onset of the disease. Diseases that can mimic the clinical picture of polymyalgia rheumatica are neoplasia, infections, metabolic disorders of the bone and endocrine diseases.

scholarly journals Challenges in the Diagnosis of Giant Cell Arteritis Before Visual Loss

2020 ◽  
pp. 1-5
Author(s):  
Purnima Mehta ◽  
Faaiq Hassan ◽  
Muhammed Omar Qadir ◽  
Shirish Dubey ◽  
Sergio Pagliarini ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Visual Loss ◽  
Systemic Vasculitis ◽  
The Elderly ◽  
Common Type ◽  
Atypical Presentation ◽  
Delay In Diagnosis ◽  
Atypical Presentations ◽  
High Index Of Suspicion

Background: Giant cell arteritis (GCA) is the most common type of systemic vasculitis affecting the elderly. Ophthalmic presentations of GCA in particular can be difficult to identify prior to permanent visual loss occurring. Methods: Here, we present 3 challenging cases as a retrospective series to highlight the variable presentations of GCA with ophthalmic involvement, but GCA was not suspected due to atypical presentation. Results: Unfortunately, all 3 cases went on to develop visual loss in the affected eye due to a delay in diagnosis or treatment. The authors wish to highlight the challenges posed to the referring clinicians, when patients had systemic/ocular co-morbidities, which delayed the suspicion of GCA Conclusion with a Practical Point: Our cases highlight the variable presentations of this condition as well as the devastating ophthalmic implications that GCA can have. A high index of suspicion must be maintained; particularly in elderly patients with atypical presentations.

Polymyalgia Rheumatica, Giant Cell Arteritis, and Vascular Complications

2017 ◽  
pp. 23-38
Author(s):  
Viera Štvrtinová ◽  
Denisa Čelovská ◽  
Svetoslav Štvrtina ◽  
Jozef Rovenský
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Polymyalgia Rheumatica ◽  
Vascular Complications

scholarly journals Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway

2017 ◽  
Vol 44 (3) ◽  
pp. 1174-1187 ◽  
Author(s):  
Artur Rozentsvit ◽  
Kevin Vinokur ◽  
Sherin Samuel ◽  
Ying Li ◽  
A. Martin Gerdes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Protective Effect ◽  
High Glucose ◽  
Ellagic Acid ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Vascular Complications ◽  
Ros Production ◽  
Gene And Protein Expression

Background/Aims: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. Methods: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. Results: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. Conclusions: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.

Evaluation of a Shared Autoimmune Disease-associated Polymorphism of TRAF6 in Systemic Sclerosis and Giant Cell Arteritis

2012 ◽  
Vol 39 (6) ◽  
pp. 1275-1279 ◽  
Author(s):  
F. DAVID CARMONA ◽  
AURORA SERRANO ◽  
LUIS RODRÍGUEZ-RODRÍGUEZ ◽  
JOSÉ LUIS CALLEJAS ◽  
CARMEN P. SIMEÓN ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Lupus Erythematosus ◽  
Genetic Network ◽  
Healthy Controls ◽  
Nucleotide Polymorphism ◽  
Common Risk Factor ◽  
Single Nucleotide

Objective.We evaluated whether a single-nucleotide polymorphism (SNP) of theTRAF6gene previously associated with systemic lupus erythematosus and rheumatoid arthritis may be a common risk factor for systemic sclerosis (SSc) and giant cell arteritis (GCA).Methods.A total of 1185 patients with SSc, 479 patients with biopsy-proven GCA, and 1442 unrelated healthy controls of white Spanish origin were genotyped for the rs540386 variant using a specifically designed TaqMan©allele discrimination assay.Results.No significant associations of this SNP with global SSc or GCA were found. This was also the case when the potential associations of theTRAF6polymorphism with the main clinical phenotypes of the 2 diseases (e.g., limited cutaneous and diffuse cutaneous SSc, or presence of polymyalgia rheumatica and visual ischemic manifestations in GCA) were assessed.Conclusion.Our data do not support a role of the rs540386TRAF6variant as a key component of the genetic network underlying SSc and GCA.

scholarly journals Sustained Elevation of Systemic Oxidative Stress and Inflammation in Exacerbation and Remission of Asthma

ISRN Allergy ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Judith C. W. Mak ◽  
Siu P. Ho ◽  
Alice S. S. Ho ◽  
Barbara K. W. Law ◽  
Amy H. K. Cheung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Exacerbation ◽  
Plasma Levels ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Systemic Oxidative Stress ◽  
Valid Index ◽  
Zymographic Analysis ◽  
Biomarkers Of Oxidative Stress

Oxidative stress has been implicated in the pathogenesis of asthma. We aimed at investigating the biomarkers of oxidative stress, inflammation, and tissue damage in patients with asthma in acute exacerbation and remission. We recruited 18 asthmatics admitted to hospital with acute exacerbation and 18 healthy nonsmoking controls matched for age. We evaluated plasma levels of 8-isoprostane, C-reactive protein (CRP) and total matrix metalloproteinase- (MMP-) 9 by ELISA, and MMP-9 activity by zymographic analysis. Plasma levels of 8-isoprostane and CRP were significantly elevated in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls. The activities of pro-MMP-9 were also significantly higher in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls in parallel to plasma levels of total MMP-9. These data suggest that overproduction of MMP-9 along with highly elevated levels of oxidative stress and inflammation is implicated in asthma exacerbation and that measurements of these biomarkers can be a valid index in its management.

scholarly journals Giant Cell Arteritis: From Neurologist’s Perspective

2021 ◽  
Author(s):  
Ravish Rajiv Keni ◽  
M. Sowmya ◽  
Sreekanta Swamy
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Visual Loss ◽  
Multidisciplinary Care ◽  
The Elderly ◽  
External Carotid Artery ◽  
Laboratory Evaluation ◽  
High Dose ◽  
Granulomatous Vasculitis ◽  
Dose Corticosteroid

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large- and medium-sized arteries in the elderly and potentially causes visual loss. In an elderly patient presenting with acute pain in the distribution of the external carotid artery (e.g., headache, scalp tenderness); polymyalgia rhematica; or acute/transient visual loss or diplopia; a possibility of GCA should be considered in one of the differential diagnosis. Urgent laboratory evaluation (e.g., ESR, CRP, platelet count), followed immediately by empiric high-dose corticosteroid therapy is warranted in patients suspected of having GCA. Although ultrasound techniques are sensitive for the diagnosis of GCA, TAB remains the best confirmatory test. Patients with GCA often require long durations of steroid therapy and steroid-related complications are common. Multidisciplinary care and the use of steroid-sparing regimens are warranted in case of relapse.

scholarly journals Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2022
Author(s):  
Larissa E. van Eijk ◽  
Adriana Tami ◽  
Jan-Luuk Hillebrands ◽  
Wilfred F. A. den Dunnen ◽  
Martin H. de Borst ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Options ◽  
Critical Role ◽  
Healthy Controls ◽  
Serum Samples ◽  
Discriminative Ability ◽  
Discriminative Performance ◽  
Serum Free ◽  
Free Thiol ◽  
Systemic Oxidative Stress

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

A Nonsynonymous Functional Variant of the ITGAM Gene Is Not Involved in Biopsy-proven Giant Cell Arteritis

2011 ◽  
Vol 38 (12) ◽  
pp. 2598-2601 ◽  
Author(s):  
F. DAVID CARMONA ◽  
AURORA SERRANO ◽  
LUIS RODRÍGUEZ-RODRÍGUEZ ◽  
SANTOS CASTAÑEDA ◽  
JOSÉ A. MIRANDA-FILLOY ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Clinical Manifestations ◽  
Healthy Controls ◽  
Functional Variant ◽  
Allele Discrimination ◽  
Control Set ◽  
Spanish Cohort ◽  
White Patients

Objective.To investigate whether a functional integrin alpha M (ITGAM) variant is involved in susceptibility to and clinical manifestations of giant cell arteritis (GCA).Methods.A Spanish cohort of 437 white patients with biopsy-proven GCA and 1388 healthy controls were genotyped using the TaqMan allele discrimination technology.Results.No association was observed between ITGAM rs1143679 and GCA (p = 0.80, OR 0.97). Similarly, subphenotype analyses did not yield significant differences between the case subgroups and the control set or between GCA patients with or without the main specific features of GCA.Conclusion.Our results suggest that the ITGAM rs1143679 variant does not play an important role in the pathophysiology of GCA.

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