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Enhanced endothelium-dependent vasodilation in Fabry disease
G Altarescu1, D F Moore, R Pursley
1Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1260, USA.
Stroke
|July 7, 2001
Summary
Patients with Fabry disease exhibit heightened vascular reactivity, particularly in forearm blood flow responses to acetylcholine. This suggests altered endothelial function, impacting blood vessel regulation in this genetic disorder.
Area of Science:
- Vascular Biology
- Genetics
- Metabolic Disorders
Background:
- Fabry disease is an X-linked lysosomal storage disorder caused by alpha-galactosidase A deficiency.
- Glycolipid accumulation, especially globotriaosylceramide, occurs in vascular cells, contributing to systemic vasculopathy.
- Early-onset stroke is a common complication, but its pathogenesis remains unclear.
Purpose of the Study:
- To investigate vascular reactivity in patients with Fabry disease.
- To assess endothelium-dependent vasodilation using pharmacological agents.
- To explore potential alterations in nitric oxide (NO)-independent pathways.
Main Methods:
- Venous plethysmography was used to measure forearm blood flow in 17 Fabry patients and 13 controls.
- Acetylcholine and sodium nitroprusside were infused intra-arterially, with and without N(G)-monomethyl-L-arginine (L-NMMA).
- Measurements were taken at baseline and during infusions to assess vascular responses.
Main Results:
- Fabry patients showed significantly higher forearm blood flow than controls at all acetylcholine doses.
- Patients exhibited a greater vasodilatory response to acetylcholine, even when nitric oxide synthesis was inhibited by L-NMMA.
- These findings indicate enhanced endothelium-mediated vascular reactivity.
Conclusions:
- Fabry disease is associated with increased endothelium-mediated vascular reactivity.
- The augmented response to acetylcholine, independent of L-NMMA, suggests dysfunction in non-NO-dependent vasodilatory pathways.
- These vascular alterations may contribute to the pathogenesis of vasculopathy in Fabry disease.