α-Galactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency
PF Bodary, Y Shen, FB Vargas, X Bi, KA Ostenso… - Circulation, 2005 - Am Heart Assoc
Circulation, 2005•Am Heart Assoc
Background—α-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. Methods and
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 …
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. Methods and
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 …
Background— α-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.
Methods and 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.
Am Heart Assoc