Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome

Marfan syndrome (MFS) is an autosomal-dominant disorder of connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mortality is often due to aortic dissection and rupture. Weinvestigated the structural and functional properties of the heart and aorta in a [Fbn1C1039G/+] MFS mouse using high-resolution ultrasound (echo) and optical coherence tomography (OCT). Echo was performed on 6- and 12-month old wild type (WT) and MFS mice (n = 8). In vivo pulse wave velocity (PWV), aortic root diameter, ejection fraction, stroke volume, left ventricular (LV) wall thickness, LV mass and mitral valve early and atrial velocities (E/A) ratio were measured by high resolution echocardiography. OCT was per- formed on 12-month oldWTand MFS fixed mouse hearts to measure ventricular volume and mass. ThePWVwas significantly increased in 6-mo MFS vs.WT(366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p = 0.003) and 12-mo MFS vs.WT(459.5 ± 42.3 vs. 205.3 ± 30.3 cm/s; p< 0.0001). PWVincreased with age in MFS mice only.Wealso found a significantly enlarged aortic root and decreased E/A ratio in MFS mice compared withWTfor both age groups. The [Fbn1C1039G/+] mouse model of MFS replicates many of the anomalies of Mar- fan patients including significant aortic dilation, central aortic stiffness, LV systolic and dia- stolic dysfunction. This is the first demonstration of the direct measurement in vivo of pulse wave velocity non-invasively in the aortic arch of MFS mice, a robust measure of aortic stiffness and a critical clinical parameter for the assessment of pathology in the Marfan syndrome.