Abstract Body: Introduction: Marfan Syndrome (MFS) is a relatively common connective tissue disorder with an incidence in 1 in 5000 persons secondary to mutations in the extra-cellular protein Fibrillin-1. MFS has long been characterized as a classic Transforming Growth Factor Beta aortopathy. We and others have found that thoracic aorta aneurysm (TAA) formation in MFS is secondary to multiple converging pathways including aberrant ligand-independent angiotensin Type 1A receptor (AT1R) activation. Deciphering the discrete pathways is essential to improve pharmacologic treatment for patients with MFS.

Hypothesis: Inflammation is an independent and upstream pathway in TAA formation in MFS.

Methods: Cross-sections of ascending aorta of Fbn1^mgR/mgR mice and wild-type (WT) littermates were examined for infiltration by macrophages and CD4+ t-cells, every 4 weeks after birth through 4 months. A subset of Fbn1^mgR/mgR mice were administered losartan, an AT1R antagonist, from 2 weeks after birth until 8 weeks of life to evaluate whether AT1R activation is required for or independent of inflammatory cell infiltration, assessed by histomorphometry and inflammatory cell infiltration.

Results: Macrophage infiltration of aortas occurs early and persists through postnatal development in Fbn1^mgR/mgR but not WT littermate mice, whereas CD4+ T-cells increase in abundance between 3 and 4 months after birth. Treatment with losartan, which reduces elastin degradation, does not alter inflammatory cell infiltration.

Conclusions: Our data suggest that TAA progression is associated with inflammatory cell infiltration, which occurs independently of aberrant AT1R activation in MFS. We believe inflammatory cell infiltration presents a novel pathway for a multimodal approach to prevent TAA progression in MFS.