The role of type I collagen in aortic wall strength with a homotrimeric [alpha 1(I)](3) collagen mouse model

Purpose: Elastin and collagen (types I and III) are the primary load-bearin g elements in aortic tissue. Deficiencies and derangements in elastin and t ype III collagen have been associated with the development of aneurysmal di sease. However, the role of type I collagen is less well defined. The purpo se of this study was to define the role of type I collagen in maintaining b iomechanical integrity in the thoracic aorta, with a mouse model that produ ces homotrimeric type I collagen [alpha1(I)](3), rather than the normally p resent heterotrimeric [alpha1(I)](2) alpha2(I) type I collagen isotype. Methods: Ascending and descending thoracic aortas from homozygous (oim/oim) , heterozygous (oim/+), and wildtype (+/+) mice were harvested. Circumferen tial and longitudinal load-extension curves were used as a means of determi ning maximum breaking strength (P-max) and incremental elastic modulus (IEM ). Histologic analyses and hydroxyproline assays were performed as a means of determining collagen organization and content. Results: Circumferentially, the ascending and descending aortas of oim/oim mice demonstrated significantly reduced F-max with an F-max of only 60% and 23%, respectively, of wildtype mice aortas. Oim/oim descending aortas demo nstrated significantly greater compliance (decreased IEM), and the ascendin g aortas also exhibited a trend toward increased compliance. Reduced breaki ng strength was also demonstrated with longitudinal extension of the descen ding aorta. Conclusion: The presence of homotrimeric type I collagen isotype (absence o f alpha2(I) collagen) significantly weakens the aorta. This study demonstra tes the integral role of type I collagen in the biomechanical and functiona l properties of the aorta and may help to elucidate the role of collagen in the development of aneurysmal aortic disease or dissection.