Abstract 467: Differences In Susceptibility to Abdominal Aortic Aneurysms Between 129/SvEv and C57Bl/6 Mice

Abstract

Objective: Abundant evidence has demonstrated the profound influence of genetic background on cardiovascular phenotypes. Previous work in the mouse has shown that genetic background-related variations in murine models of Marfan syndrome affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. Marfan syndrome mice in the C57Bl/6 genetic background are less susceptible to aneurysm formation compared to 129/SvEv mice. In this study, we hypothesize that the susceptibility to the development of abdominal aortic aneurysm (AAA) will be similarly increased in 129/SvEv mice compared to C57Bl/6 mice. Approach and Results: Mice of either C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Aortic diameters were measured at 6 weeks post induction. Aneurysm size was significantly larger in 129/SvEv mice than in C57Bl/6 mice. Histological studies showed more severe elastic lamella disruption and fragmentation in 129/SvEv mice than in C57Bl/6 mice. Macrophage infiltration was more prominent in the aortas of 129/SvEv mice than of C57Bl/6 mice. The elastic modulus was found to be higher in the aortas of the 129/SvEv mice compared to the C57Bl/6 mice. MMP-2 and MMP-9 levels, examined by gelatin zymography,were higher in the aortas of 129/SvEv mice compared to the C57Bl/6 mice. Conclusions: These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. The difference in the susceptibility to AAA is at least partially due to the difference in aortic elastic lamellae mechanical properties and MMP-2 and -9 expression between the two strains of mice.