Abstract 104: Aortic Dilation and Elasticity in Thoracic Aortic Aneurysm in a Marfan Model is Sexually Dimorphic

Objective: Meta-analysis of data derived from Marfan patients in the Genetically-Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) consortium revealed that thoracic aortic aneurysms occur more frequently in men than in women. To determine the characteristics of sexual dimorphism in experimental thoracic aortic aneurysms of a Marfan model, we determined ascending aortic and aortic root morphology in male and female fibrillin-1 haploinsufficent (FBN1 C1041G/+) mice using ultrasonography. Method and Results: Aortas from 4 to 6 week old male and female FBN1 C1041G/+ mice and their wild type littermates were assessed by high frequency ultrasonography. Mice were anesthetized and maintained at a heart rate of 450-550 beats per minute. Ultrasound images were captured using a Vevo 3100 instrument with a 40 MHz tranducer. The maximal luminal diameter of ascending aortic between the sinotubular junction and the innominate artery, and the aortic root diameter at the sinus of valsalva, were measured in mid-systole and end-diastole by two independent observers who were blinded to mice identity. FBN1 C1041G/+ mice demonstrated greater ascending aortic dilation in male mice compared to female mice, whereas no difference in aortic root diameter were detected between male and female wild type littermates. In addition, modest ascending aortic dilation was detected before aortic root dilation in FBN1 C1041G/+ mice. Ascending aortas from FBN1 C1041G/+ mice also demonstrated loss of elasticity as evidenced by reduced expansion in systole. Interestingly, this difference was detected much earlier than expected. Conclusion: The fibrillin-1 haploinsufficent model of Marfan syndrome associated thoracic aortic aneurysm demonstrate sexual dimorphism in ascending aortic dilation. Loss of elasticity in the ascending aorta is also an early manifestation in this thoracic aortic aneurysm model.