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Vascular defects in mice with mutation in the Lysosomal Trafficking Regulator gene
Author(s) -
Beyer andreas M.,
Trantow Colleen,
Anderson Michael G,
Rahmouni Kamal
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1148.14
Subject(s) - mutant , acetylcholine , regulator , endothelial dysfunction , atrophy , aorta , chemistry , medicine , endocrinology , gene , vascular smooth muscle , vascular tissue , pathology , biology , biochemistry , botany , smooth muscle
Exfoliation (XFS) is commonly associated with disturbance in elasticity, oxidative stress and increased risk for aortic aneurism. We hypothesized that vascular defects may be common in XFS which could contribute to the vascular disorders associated with this condition. To test this, we studied the vascular function and structure of a mouse model that recapitulates many phenotypes of human XFS: mice that carry a mutation in the lysosomal trafficking regulator ( Lyst ) gene. Using aorta rings, we found an attenuated relaxation to acetylcholine in Lyst bg‐J mice (50±16%, n=3) as compared to B6 controls (65±7%, n=3) indicating that mutation in the Lyst gene leads to endothelial dysfunction. Histological analysis of the vessels showed a decrease in vascular cross section area in Lyst bg‐J mice (0.1022±0.0104 μm 2 ) as compared to controls (0.1291±0.0009 μm 2 , P<0.05) demonstrating vascular atrophy in the mutant mice. In addition, Lyst bg‐J mice exhibit vascular wall thinning. In conclusion, mutation in the Lyst gene in mice results in vascular defects which may account for the disorders associated with XFS in human. Presence of vascular atrophy is consistent with the attenuated aortic relaxation to acetylcholine because vascular atrophy is known to attenuate the endothelial responses to stimuli. Finally, wall thinning is consistent with the increased risk for aortic aneurisms associated with XFS.