title: Alpha-galactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency.
abstract: BACKGROUND
  Alpha-galactosidase A (Gla) deficiency leads to widespread tissue accumulation of neutral glycosphingolipids and is associated with premature vascular complications such as myocardial infarction and stroke. Glycosphingolipids have been shown to accumulate in human atherosclerotic lesions, although their role in atherogenesis is unclear.
  
  
  RESULTS
  To determine whether Gla affects the progression of atherosclerosis, mice were generated with combined deficiencies of apolipoprotein E and Gla. At 45 weeks of age, Gla-deficient mice had developed more atherosclerosis than mice with normal Gla expression (25.1+/-14.0 versus 12.3+/-9.3 mm2 of total lesion area, P<0.02). This increase in atherosclerosis was associated with the presence of increased Gb3, enhanced inducible nitric oxide synthase expression, and increased nitrotyrosine staining.
  
  
  CONCLUSIONS
  These findings suggest that deficiency of Gla leads to increased inducible nitric oxide synthase expression and accelerated atherosclerosis.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical Center, Ann Arbor, Mich, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bodary
authors.forename: Yuechun
authors.initials: Y
authors.lastname: Shen
authors.forename: Fernando B
authors.initials: FB
authors.lastname: Vargas
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Bi
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Ostenso
authors.forename: Shufang
authors.initials: S
authors.lastname: Gu
authors.forename: James A
authors.initials: JA
authors.lastname: Shayman
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D000795:Fabry Disease / Q000150:complications*; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D000519:alpha-Galactosidase