Title
Alpha 2(I) collagen deficient oim mice have altered biomechanical integrity, collagen content, and collagen crosslinking of their thoracic aorta
Author
Pfeiffer, B.J.
Franklin, C.L.
Hsieh, F.H.
Bank, R.A.
Phillips, C.L.
TNO Preventie en Gezondheid
Publication year
2005
Abstract
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 (Fmax) 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 Fmax 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. © 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved. Chemicals / CAS: hydroxyproline, 51-35-4, 6912-67-0; pyridinoline, 63800-01-1; Collagen Type I; Collagen, 9007-34-5
Subject
Biomechanics
Crosslinks
Oim
Type I collagen
functional group
hydroxyproline
pyridinoline
animal cell
animal model
animal tissue
artery disease
ascending aorta
biomechanics
blood vessel parameters
controlled study
descending aorta
evaluation
gene mutation
heterozygote
histology
molecule
morphological trait
mouse
mouse strain
nonhuman
osteogenesis imperfecta
priority journal
protein content
protein cross linking
protein deficiency
protein function
staining
thoracic aorta
wild type
Animals
Aorta, Thoracic
Biomechanics
Collagen
Collagen Type I
Mice
Mice, Mutant Strains
Osteogenesis Imperfecta
To reference this document use:
http://resolver.tudelft.nl/uuid:53702114-92a8-4eec-83e0-32d399ed16a9
DOI
https://doi.org/10.1016/j.matbio.2005.07.001
TNO identifier
238756
ISSN
0945-053X
Source
Matrix Biology, 24 (7), 451-458
Document type
article