BACKGROUND AND PURPOSE: Fabry disease is an X-linked lysosomal storage disease secondary to deficiency of alpha-galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide in arterial smooth muscle and endothelial cells. A systemic vasculopathy, including early-onset stroke, is prevalent without a clear pathogenesis. METHODS: Seventeen normotensive and normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13 control subjects (aged 21 to 48 years) were investigated by venous plethysmography, allowing assessment of forearm blood flow. Plethysmographic measurements were obtained at baseline and during intra-arterial infusion of acetylcholine and sodium nitroprusside both with and without N(G)-monomethyl-L-arginine (L-NMMA). RESULTS: Forearm blood flow was significantly higher in patients than in control subjects at all 3 acetylcholine doses (P=0.014). Patients had a greater response to acetylcholine even after the addition of L-NMMA (P=0.036). CONCLUSIONS: These results demonstrate an increased endothelium-mediated vascular reactivity in Fabry disease. The increased vessel response to acetylcholine with and without L-NMMA suggests altered functionality of non-NO endothelium-dependent vasodilatory pathways.
BACKGROUND AND PURPOSE:Fabry disease is an X-linked lysosomal storage disease secondary to deficiency of alpha-galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide in arterial smooth muscle and endothelial cells. A systemic vasculopathy, including early-onset stroke, is prevalent without a clear pathogenesis. METHODS: Seventeen normotensive and normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13 control subjects (aged 21 to 48 years) were investigated by venous plethysmography, allowing assessment of forearm blood flow. Plethysmographic measurements were obtained at baseline and during intra-arterial infusion of acetylcholine and sodium nitroprusside both with and without N(G)-monomethyl-L-arginine (L-NMMA). RESULTS: Forearm blood flow was significantly higher in patients than in control subjects at all 3 acetylcholine doses (P=0.014). Patients had a greater response to acetylcholine even after the addition of L-NMMA (P=0.036). CONCLUSIONS: These results demonstrate an increased endothelium-mediated vascular reactivity in Fabry disease. The increased vessel response to acetylcholine with and without L-NMMA suggests altered functionality of non-NO endothelium-dependent vasodilatory pathways.
Authors: T DeGraba; S Azhar; F Dignat-George; E Brown; B Boutière; G Altarescu; R McCarron; R Schiffmann Journal: Ann Neurol Date: 2000-02 Impact factor: 10.422
Authors: K Utsumi; N Yamamoto; R Kase; T Takata; T Okumiya; H Saito; T Suzuki; E Uyama; H Sakuraba Journal: Intern Med Date: 1997-05 Impact factor: 1.271
Authors: A Huang; D Sun; C J Smith; J A Connetta; E G Shesely; A Koller; G Kaley Journal: Am J Physiol Heart Circ Physiol Date: 2000-03 Impact factor: 4.733
Authors: Hasan Askari; Christine R Kaneski; Cristina Semino-Mora; Priya Desai; Agnes Ang; David E Kleiner; Lorah T Perlee; Martha Quezado; Linda E Spollen; Brandon A Wustman; Raphael Schiffmann Journal: Virchows Arch Date: 2007-08-03 Impact factor: 4.064
Authors: T Kovarnik; G S Mintz; D Karetova; J Horak; J Bultas; R Skulec; H Skalicka; M Aschermann; M Elleder; A Linhart Journal: J Inherit Metab Dis Date: 2008-11-08 Impact factor: 4.982
Authors: Marieke Biegstraaten; Ivo N van Schaik; Wouter Wieling; Frits A Wijburg; Carla E M Hollak Journal: BMC Neurol Date: 2010-06-07 Impact factor: 2.474
Authors: Jin-Song Shen; Xing-Li Meng; David F Moore; Jane M Quirk; James A Shayman; Raphael Schiffmann; Christine R Kaneski Journal: Mol Genet Metab Date: 2008-08-15 Impact factor: 4.797