Journal
MATRIX BIOLOGY
Volume 24, Issue 7, Pages 451-458Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.matbio.2005.07.001
Keywords
type I collagen; oim; aorta; biomechanics; crosslinks
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Funding
- NIA NIH HHS [1R03AG19475] Funding Source: Medline
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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 alpha 1(I) and one alpha 2(I) collagen chains, alpha 1(I)(2)alpha 2(I). Recent investigations have reported that patients with recessively inherited forms of Ehlers Danlos syndrome that fail to synthesize pro alpha 2(I) chains have increased risks of cardiovascular complications. To assess the role of alpha 2(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, alpha 1(I)(3). We evaluated thoracic aortas from 3-month-old oim, heterozygote, and wildlype 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 alpha 2(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. (c) 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved.
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