Cargando…
Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement?
Fabry disease is an X-linked lysosomal storage disease caused by mutations in the GLA gene that lead to a reduction or an absence of the enzyme α-galactosidase A, resulting in the progressive and multisystemic accumulation of globotriaosylceramide. Clinical manifestation varies from mild to severe,...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262438/ https://www.ncbi.nlm.nih.gov/pubmed/30400144 http://dx.doi.org/10.3390/jcm7110409 |
_version_ | 1783375106221801472 |
---|---|
author | Ravarotto, Verdiana Simioni, Francesca Carraro, Gianni Bertoldi, Giovanni Pagnin, Elisa Calò, Lorenzo A. |
author_facet | Ravarotto, Verdiana Simioni, Francesca Carraro, Gianni Bertoldi, Giovanni Pagnin, Elisa Calò, Lorenzo A. |
author_sort | Ravarotto, Verdiana |
collection | PubMed |
description | Fabry disease is an X-linked lysosomal storage disease caused by mutations in the GLA gene that lead to a reduction or an absence of the enzyme α-galactosidase A, resulting in the progressive and multisystemic accumulation of globotriaosylceramide. Clinical manifestation varies from mild to severe, depending on the phenotype. The main clinical manifestations are cutaneous (angiokeratomas), neurological (acroparesthesias), gastrointestinal (nausea, diarrhea abdominal pain), renal (proteinuria and kidney failure), cardiovascular (cardiomyopathy and arrhythmias), and cerebrovascular (stroke). A diagnosis of Fabry disease can be made with an enzymatic assay showing absent or reduced α-galactosidase A in male patients, while in heterozygous female patients, molecular genetic testing is needed. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is nowadays the most-used disease-specific therapeutic option. Despite ERT, cardiocerebrovascular-renal irreversible organ injury occurs, therefore additional knowledge and a deeper understanding of further pathophysiological mechanisms leading to end organ damage in Fabry disease are needed. Recent data point toward oxidative stress, oxidative stress signaling, and inflammation as some such mechanisms. In this short review, the current knowledge on the involvement of oxidative stress in cardiovascular-renal remodeling is summarized and related to the most recent evidence of oxidative stress activation in Fabry disease, and clearly points toward the involvement of oxidative stress in the pathophysiology of the medium- to long-term cardiovascular-renal damage of Fabry disease. |
format | Online Article Text |
id | pubmed-6262438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62624382018-12-03 Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? Ravarotto, Verdiana Simioni, Francesca Carraro, Gianni Bertoldi, Giovanni Pagnin, Elisa Calò, Lorenzo A. J Clin Med Review Fabry disease is an X-linked lysosomal storage disease caused by mutations in the GLA gene that lead to a reduction or an absence of the enzyme α-galactosidase A, resulting in the progressive and multisystemic accumulation of globotriaosylceramide. Clinical manifestation varies from mild to severe, depending on the phenotype. The main clinical manifestations are cutaneous (angiokeratomas), neurological (acroparesthesias), gastrointestinal (nausea, diarrhea abdominal pain), renal (proteinuria and kidney failure), cardiovascular (cardiomyopathy and arrhythmias), and cerebrovascular (stroke). A diagnosis of Fabry disease can be made with an enzymatic assay showing absent or reduced α-galactosidase A in male patients, while in heterozygous female patients, molecular genetic testing is needed. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is nowadays the most-used disease-specific therapeutic option. Despite ERT, cardiocerebrovascular-renal irreversible organ injury occurs, therefore additional knowledge and a deeper understanding of further pathophysiological mechanisms leading to end organ damage in Fabry disease are needed. Recent data point toward oxidative stress, oxidative stress signaling, and inflammation as some such mechanisms. In this short review, the current knowledge on the involvement of oxidative stress in cardiovascular-renal remodeling is summarized and related to the most recent evidence of oxidative stress activation in Fabry disease, and clearly points toward the involvement of oxidative stress in the pathophysiology of the medium- to long-term cardiovascular-renal damage of Fabry disease. MDPI 2018-11-02 /pmc/articles/PMC6262438/ /pubmed/30400144 http://dx.doi.org/10.3390/jcm7110409 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Ravarotto, Verdiana Simioni, Francesca Carraro, Gianni Bertoldi, Giovanni Pagnin, Elisa Calò, Lorenzo A. Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? |
title | Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? |
title_full | Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? |
title_fullStr | Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? |
title_full_unstemmed | Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? |
title_short | Oxidative Stress and Cardiovascular-Renal Damage in Fabry Disease: Is There Room for a Pathophysiological Involvement? |
title_sort | oxidative stress and cardiovascular-renal damage in fabry disease: is there room for a pathophysiological involvement? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262438/ https://www.ncbi.nlm.nih.gov/pubmed/30400144 http://dx.doi.org/10.3390/jcm7110409 |
work_keys_str_mv | AT ravarottoverdiana oxidativestressandcardiovascularrenaldamageinfabrydiseaseisthereroomforapathophysiologicalinvolvement AT simionifrancesca oxidativestressandcardiovascularrenaldamageinfabrydiseaseisthereroomforapathophysiologicalinvolvement AT carrarogianni oxidativestressandcardiovascularrenaldamageinfabrydiseaseisthereroomforapathophysiologicalinvolvement AT bertoldigiovanni oxidativestressandcardiovascularrenaldamageinfabrydiseaseisthereroomforapathophysiologicalinvolvement AT pagninelisa oxidativestressandcardiovascularrenaldamageinfabrydiseaseisthereroomforapathophysiologicalinvolvement AT calolorenzoa oxidativestressandcardiovascularrenaldamageinfabrydiseaseisthereroomforapathophysiologicalinvolvement |