The role of type I collagen in aortic wall strength with a homotrimeric [α1(I)]3 collagen mouse model

Abstract

Purpose: Elastin and collagen (types I and III) are the primary load-bearing elements in aortic tissue. Deficiencies and derangements in elastin and type III collagen have been associated with the development of aneurysmal disease. However, the role of type I collagen is less well defined. The purpose of this study was to define the role of type I collagen in maintaining biomechanical integrity in the thoracic aorta, with a mouse model that produces homotrimeric type I collagen [α1(I)]3, rather than the normally present heterotrimeric [α1(I)]2 α2(I) type I collagen isotype. Methods: Ascending and descending thoracic aortas from homozygous (oim/oim), heterozygous (oim/+), and wildtype (+/+) mice were harvested. Circumferential and longitudinal load-extension curves were used as a means of determining maximum breaking strength (Fmax) 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 Fmax, with an Fmax of only 60% and 23%, respectively, of wildtype mice aortas. Oim/oim descending aortas demonstrated significantly greater compliance (decreased IEM), and the ascending aortas also exhibited a trend toward increased compliance. Reduced breaking strength was also demonstrated with longitudinal extension of the descending aorta. Conclusion: The presence of homotrimeric type I collagen isotype (absence of α2(I) collagen) significantly weakens the aorta. This study demonstrates the integral role of type I collagen in the biomechanical and functional properties of the aorta and may help to elucidate the role of collagen in the deveopment of aneurysmal aortic disease or dissection.