3-Nitrotyrosine as a biomarker for vascular involvement in Fabry disease

Joly, Dominique; Grünfeld, Jean‐Pierre

doi:10.1038/ki.2014.126

Cited by 9 publications

(5 citation statements)

References 8 publications

(33 reference statements)

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“…3-NT has been used as a biomarker of nitrative damage in vivo [ 21 ]. The presence of 3-NT was previously reported in some carcinomas [ 22 ], in ccRCC through immunohistochemically staining, in contrast nephropathy [ 23 ], as a biomarker for vascular involvement in Fabry disease [ 24 ], and in preeclampsia [ 25 ].…”

Section: Introductionmentioning

confidence: 96%

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

et al. 2020

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Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period of three years and included 55 patients with localized renal cell carcinoma and 30 heathy subjects. Glycosylation, nitration and carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation and proteolytic cleavage were evaluated in the serum of the evaluated subjects in the present study. Our results showed some characteristics for early ccRCC: high production of cytokines, substrate hypersialylation, induced nitrosative and carbonylic stress, arginine hypermethylation, thiol/disulfide homeostasis (TDH) alteration, the regulatory role of soluble receptors (sRAGE—soluble receptor for advanced glycation end products, sIL-6R—soluble receptor for Interleukin 6) in RAGE and IL-6 signaling, the modulatory effect of TK1—thymidine kinase 1 and TuM2-PK—tumoral pyruvate-kinase 2 in controlling the level of phosphometabolites in neoplastic cells. These data could be the initial point for development of a panel of biomarkers such as total sialic acid, orosomucoids, nitrotyrosine, carbonylic metabolites, Asymmetric Dimethylarginines (ADMA), Symmetric Dimethylarginines (SDMA), and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease posttranslational modification signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis.

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Section: Introductionmentioning

confidence: 96%

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

et al. 2020

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“…Significance of XO-induced endothelial dysfunction is further supported by studies in which treatment with higher doses of allopurinol led to improved endothelial function [41–44]. Endothelial dysfunction is apparently a feature frequently seen in FD and appears to be closely linked to elevated levels of myeloperoxidase, excessive production of ROS and endothelial nitric oxide synthase uncoupling [45,46]. …”

Section: Discussionmentioning

confidence: 99%

Uric Acid as a Marker of Mortality and Morbidity in Fabry Disease

et al. 2016

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BackgroundSerum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD).ObjectivesTo evaluate the association between serum UA levels and mortality and morbidity in FD.Materials and MethodsWe conducted a post-hoc analysis of a prospectively followed-up cohort of 124 patients with genetically proven FD. Serum UA levels were acquired at baseline; clinical events and mortality were assessed during regular visits every 6 to 12 months. The primary endpoint was a composite of multiple secondary outcomes: all-cause mortality, adverse cardiovascular events, progression of renal dysfunction and stroke or transient ischaemic attack (TIA). Predictive value was assessed using the Cox proportional hazards model and the Kaplan Meyer estimator.ResultsDuring follow-up of 7.4 ± 3.7 years, 64 (52%) patients reached the primary combined endpoint. Overall, UA levels were significantly associated with combined outcome (p < 0.001) and remained independently associated after correcting for age, sex and estimated glomerular filtration rate (hazard ratio [HR] per 20 μmol/l increase 1.09, 95% confidence interval [95%CI] (1.00–1.19), p = 0.04). UA was associated with overall mortality in univariate analysis (p = 0.021); however, the association did not reach statistical significance after multivariate correction (HR per 20 μmol/l increase 1.07 95%CI 0.93–1.25, p = 0.32). Higher UA levels were also associated with cardiac adverse outcomes, progression of left ventricular hypertrophy and progression of renal dysfunction (ps < 0.001). No association was observed between UA levels and stroke or TIA (p = 0.323).Conclusion and ImplicationsIncreased serum UA levels may represent an independent risk factor for adverse clinical outcomes in Fabry patients and are associated with all-cause mortality. UA is a widely available and cheap biomarker that may improve risk stratification of Fabry patients in clinical practice.

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“…Higher proinflammatory cytokine expression has been shown during FD 31,32 . Excess of Gb3 could be the source of pro‐inflammatory signals by disturbing lipid rafts' organization and dysregulating the activation of toll‐like receptor 4 pathway, 33 leading to a pro‐inflammatory cascade and the secretion of TNF and IL‐1beta, 34,35 or to appearance of reactive oxygen species in the endothelial cell by inhibiting the NO synthase enzyme 36 . Another major pro‐inflammatory mechanism in FD is the dysregulation of autophagy 37 .…”

Section: Discussionmentioning

confidence: 99%

“… 31 , 32 Excess of Gb3 could be the source of pro‐inflammatory signals by disturbing lipid rafts' organization and dysregulating the activation of toll‐like receptor 4 pathway, 33 leading to a pro‐inflammatory cascade and the secretion of TNF and IL‐1beta, 34 , 35 or to appearance of reactive oxygen species in the endothelial cell by inhibiting the NO synthase enzyme. 36 Another major pro‐inflammatory mechanism in FD is the dysregulation of autophagy. 37 Numerous clinical observations in FD support these different models of disruption of inflammatory pathways such as the existence of AA amyloidosis, 38 histological description of myocarditis on autopsy series, 39 or reports of unexplained and prolonged fever.…”

Section: Discussionmentioning

confidence: 99%

Aseptic meningitis and Fabry disease

Montardi,

Gaudemer,

Zuber

et al. 2024

Ann Clin Transl Neurol

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ObjectiveFabry disease is caused by enzymatic defects in alpha‐galactosidase A that leads to the accumulation of glycosphingolipids throughout the body, resulting in a multisystemic disorder. The most common neurological manifestations are neuropathic pain, autonomic nervous system dysfunction and strokes, but some rarer neurological manifestations exist. Among these, aseptic meningitis is a possible complication. Our objectives were to measure the prevalence of this complication in a cohort of patients with Fabry disease, and to describe its clinical features.MethodsWe conducted a retrospective review of Fabry disease patients followed at our tertiary referral center between 1995 and September 2023 with at least one episode of meningitis, and performed a systematic review to identify similar published cases.ResultsFour patients out of 107 (3.7%) had at least one episode of aseptic meningitis. Our systematic review identified 25 other observations. The median age of these 29 patients was 29.0 years, the median cerebrospinal fluid leukocyte count was 24 cells/mm3 with a predominance of lymphocytes in 64.7% of cases. In 82.8% of the patients, the diagnosis of Fabry disease was unknown before the meningitis. Large artery stenosis was present in 17.2% of patients and 57.1% of patients had a recent stroke concomitant with the meningitis. Several differential diagnoses were evoked, such as multiple sclerosis or central nervous system vasculitis.InterpretationOur study suggests that Fabry disease should be considered as a cause of aseptic meningitis. The pathophysiological mechanisms underlying meningeal inflammation remain largely unknown but may reflect the dysregulation of pro‐inflammatory signaling pathways.

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3-Nitrotyrosine as a biomarker for vascular involvement in Fabry disease

Cited by 9 publications

References 8 publications

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

Uric Acid as a Marker of Mortality and Morbidity in Fabry Disease

Aseptic meningitis and Fabry disease

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