ArticlePloS one2012
Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Neuropsychiatric Symptoms and Their Association With Sex, Age, and Enzyme Replacement Therapy in Fabry Disease: A Systematic Review.Frontiers in psychiatry · 2022Pooled it
- Clinical manifestations, diagnosis, and management of renal involvement in Fabry disease.Renal failure · 2026Review
- Vascular endothelial dysfunction and echocardiographic changes in male and female patients with Fabry disease: a single-center observational study.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Article
- The Sphingolipid Balance and Endothelial Dysfunction in Lysosomal Storage Diseases: Shared Mechanisms in Gaucher, Niemann-Pick and Fabry Disease.International journal of molecular sciences · 2026Review
- Pathogenic mechanisms in Fabry disease.Frontiers in medicine · 2026Review
- Fabry Disease Beyond Storage: The Role of Inflammation in Disease Progression.International journal of molecular sciences · 2025Review
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- 2024 Update of the TSOC Expert Consensus of Fabry Disease.Acta Cardiologica Sinica · 2024Article
- Inflammation, Oxidative Stress, and Endothelial Dysfunction in the Pathogenesis of Vascular Damage: Unraveling Novel Cardiovascular Risk Factors in Fabry Disease.International journal of molecular sciences · 2024Review
- Oxidative stress and its role in Fabry disease.Journal of nephrology · 2024Review
- Review
- Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry's disease.Frontiers in cardiovascular medicine · 2024Article
- Infertility in Fabry's Disease: role of hypoxia and inflammation in determining testicular damage.Frontiers in endocrinology · 2024Article
- Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease.Frontiers in cardiovascular medicine · 2024Review
- Molecular Pathogenesis of Central and Peripheral Nervous System Complications in Anderson-Fabry Disease.International journal of molecular sciences · 2023Review
- JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study.European heart journal · 2023Article
- Biochemical Mechanisms beyond Glycosphingolipid Accumulation in Fabry Disease: Might They Provide Additional Therapeutic Treatments?Journal of clinical medicine · 2023Review
- Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease.The Journal of pharmacology and experimental therapeutics · 2023Article
- Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson-Fabry disease.Cell death & disease · 2021Article
- Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype.EMBO molecular medicine · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFabry disease (FD) is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA) resulting in the accumulation of globotriaosylsphingosine (Gb3) in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND
resultsIn order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs) were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs.
conclusionsDeregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.
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Registered trials
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