Abstract Background Thoracic aortic aneurysm (TAA), the abnormal widening of the thoracic aorta, can occur in isolation or as part of a connective tissue disorder like Marfan syndrome (MFS). Insulin-growth factor binding protein 2 (Igfbp2) regulates cell proliferation, growth, and extracellular matrix remodeling. Our lab identified significant upregulation of Igfbp2 in the aortic wall of three independent TAA mouse models (including Fbn1C1041G/+ (MFS)), with an 8- to 30-fold increase prior to aneurysm development, suggesting that it might drive TAA establishment. Material and methods We explored the role of upregulated Igfbp2 on TAA development and progression by crossbreeding Igfbp2+/- and Fbn1C1041G/+ mice. This breeding yielded pups belonging to four genotype groups (N = 14 per group): Fbn1+/+/Igfbp2+/-, Fbn1C1041G/+/Igfbp2+/+, Fbn1C1041G/+/Igfbp2+/-, and Fbn1+/+/Igfbp2+/+. Aortic root and ascending aorta diameters of male mice were determined every 4 weeks from 4 to 28 weeks of age via transthoracic echocardiography utilizing a Vevo-2100 system with MS550D transducer. Aortic root and ascending aorta data were analyzed separately using likelihood ratio tests and chi-squared statistics. Post-hoc analysis involved a Tukey’s HSD test. Results Our analysis confirmed exaggerated aortic growth both at the level of the aortic root and the ascending aorta in male Fbn1C1014G/+ versus wildtypes. In contrast, haplo-insufficiency for Igfbp2 alone showed no measurable effect on aortic diameter, nor did it have an impact in combination with an Fbn1C1041G/+ background. Conclusion Haplo-insufficiency for Igfbp2 in Fbn1C1041G/+ mice has no significant impact on TAA development and progression, suggesting that it may not be sufficient to mitigate aneurysm progression.
Roeck et al. (Fri,) studied this question.