title: Differential ascending and descending aortic mechanics parallel aneurysmal propensity in a mouse model of Marfan syndrome.
abstract: Marfan syndrome (MFS) is a multi-system connective tissue disorder that results from mutations to the gene that codes the elastin-associated glycoprotein fibrillin-1. Although elastic fibers are compromised throughout the arterial tree, the most severe phenotype manifests in the ascending aorta. By comparing biaxial mechanics of the ascending and descending thoracic aorta in a mouse model of MFS, we show that aneurysmal propensity correlates well with both a marked increase in circumferential material stiffness and an increase in intramural shear stress despite a near maintenance of circumferential stress. This finding is corroborated via a comparison of the present results with previously reported findings for both the carotid artery from the same mouse model of MFS and for the thoracic aorta from another model of elastin-associated glycoprotein deficiency that does not predispose to thoracic aortic aneurysms. We submit that the unique biaxial loading of the ascending thoracic aorta conspires with fibrillin-1 deficiency to render this aortic segment vulnerable to aneurysm and rupture.
authors.affiliation: Department of Biomedical Engineering Yale University, New Haven, CT, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bellini
authors.affiliation: Department of Biomedical Engineering Yale University, New Haven, CT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Korneva
authors.affiliation: Departments of Cell Biology and Medicine New York University, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zilberberg
authors.affiliation: Department of Pharmacology and Systems Therapeutics Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: F
authors.initials: F
authors.lastname: Ramirez
authors.affiliation: Departments of Cell Biology and Medicine New York University, New York, NY, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Rifkin
authors.affiliation: Department of Biomedical Engineering Yale University, New Haven, CT, USA.|Vascular Biology and Therapeutics Program Yale School of Medicine, New Haven, CT, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Humphrey
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017545:Aortic Aneurysm, Thoracic / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D000071838:Fibrillin-1 / Q000378:metabolism; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000150:complications*; D055595:Mechanical Phenomena; D051379:Mice; D013314:Stress, Mechanical; D016474:Weight-Bearing
chemical_list: D000071838:Fibrillin-1; D004549:Elastin
keywords: Elastic fiber fragmentation; Fibrillin-1; Stiffness; Stress; Thoracic aortic aneurysm