Aortic Strain Correlates With Elastin Fragmentation in Fibrillin-1 Hypomorphic Mice

Background: High-frequency ultrasound has facilitated in vivo measurement of murine ascending aorta, allowing aortic strain to be determined from 2-D imaging. Thoracic aortic aneurysms associated with mutations in fibrillin-1 (FBN1) display elastin fragmentation, which may affect aortic strain. In this study, we determined the relationship between elastin fragmentation and aortic circumferential strain in wild-type (WT) and fibrillin-1 hypomorphic (FBN1(mgR/mgR)) mice. Methods and Results: Luminal diameter of the ascending aorta from WT and FBN1(mgR/mgR) mice was measured in systole and diastole. Expansion of the ascending aorta during systole in male and female WT mice was 0.21±0.02 mm (16.3%) and 0.21±0.01 mm (17.0%), respectively, while expansion in male and female FBN1(mgR/mgR) mice was 0.11±0.04 mm (4.9%) and 0.07±0.02 mm (4.5%), respectively. Reduced circumferential strain was observed in FBN1(mgR/mgR) mice compared with WT littermates. Elastin fragmentation was inversely correlated to circumferential strain (R(2)=0.628, P=0.004) and significantly correlated with aortic diameter (systole, R(2)=0.397, P=0.038; diastole, R(2)=0.515, P=0.013). Conclusions: FBN1(mgR/mgR) mice had increased aortic diameter, reduced circumferential strain, and increased elastin fragmentation. Elastin fragmentation in FBN1(mgR/mgR) and their WT littermates was correlated with reduced circumferential strain.