Effects of Age, Sex, and Extracellular Matrix Integrity on Aortic Dilatation and Rupture in a Mouse Model of Marfan Syndrome

• DOI: 10.1161/atvbaha.123.319122
• Publication Date: 2023-07-20T09:00:23Z
• Authors: Dar Weiss; Bruno V. Rego; Cristina Cavinato; David S. Li; Yuki Kawamura; Nir Emuna; Jay D. Humphrey
• Keywords: Lysyl Oxidase; Elastic fiber; Fibrillin

BACKGROUND: Transmural failure of the aorta is responsible for substantial morbidity and mortality; it occurs when mechanical stress exceeds strength. The aortic root ascending are susceptible to dissection rupture in Marfan syndrome, a connective tissue disorder characterized by progressive reduction elastic fiber integrity. Whereas competent fibers endow with compliance resilience, cross-linked collagen confer stiffness We hypothesized that postnatal reductions matrix cross-linking increase aortopathy turnover rates high. METHODS: combined ex vivo biaxial testing multimodality histological examinations quantify expected age- sex-dependent structural vulnerability Fbn1 C1041G/+ versus wild-type mice without 4-week exposures β-aminopropionitrile, an inhibitor lysyl oxidase–mediated newly synthesized fibers. RESULTS: found strong β-aminopropionitrile–associated sexual dimorphism dilatation mice, correlating compromised integrity fibril organization. A lower incidence β-aminopropionitrile–exposed aortas associated increased oxidase, suggesting compensatory remodeling slows disease progression otherwise aorta. CONCLUSIONS: Collagen structure function augmented, part, oxidase female especially male which improves integrity, particularly via fibrils adventitia. Preserving or promoting may represent therapeutic target vulnerable