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Alpha 2(I) collagen deficient oim mice have altered biomechanical integrity, collagen content, and collagen crosslinking of their thoracic aorta
Ist Teil von
Matrix biology, 2005-10, Vol.24 (7), p.451-458
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2005
Quelle
MEDLINE
Beschreibungen/Notizen
Collagen and elastin are the primary determinants of vascular integrity, with elastin hypothesized to be the major contributor to aortic compliance and type I collagen the major contributor to aortic strength and stiffness. Type I collagen is normally heterotrimeric composed of two α1(I) and one α2(I) collagen chains, α1(I)
2α2(I). Recent investigations have reported that patients with recessively inherited forms of Ehlers Danlos syndrome that fail to synthesize proα2(I) chains have increased risks of cardiovascular complications. To assess the role of α2(I) collagen in aortic integrity, we used the osteogenesis imperfecta model (
oim) mouse.
Oim mice, homozygous for a COL1A2 mutation, synthesize only homotrimeric type I collagen, α1(I)
3. We evaluated thoracic aortas from 3-month-old
oim, heterozygote, and wildtype mice biomechanically for circumferential breaking strength (
F
max) and stiffness (IEM), histologically for morphological differences, and biochemically for collagen content and crosslinking. Circumferential biomechanics of
oim and heterozygote descending thoracic aortas demonstrated the anticipated reduced
F
max and IEM relative to wildtype mice. Histological analyses of
oim descending aortas demonstrated reduced collagen staining relative to wildtype aortas suggesting decreased collagen content, which hydroxyproline analyses of ascending and descending
oim aortas confirmed. These findings suggest the reduced
oim thoracic aortic integrity correlates with the absence of the α2(I)collagen chains and in part with reduced collagen content. However,
oim ascending aortas also demonstrated a significant increase in pyridinoline crosslinks/collagen molecule as compared to wildtype ascending aortas. The role of increased collagen crosslinks is uncertain; increased crosslinking may represent a compensatory mechanism for the decreased integrity.