Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, 
caused by mutations of the microfibrillar protein fibrillin-1, that predisposes 
affected individuals to aortic aneurysm and rupture and is associated with 
increased TGFβ signaling. TGFβ is secreted from cells as a latent complex 
consisting of TGFβ, the TGFβ propeptide, and a molecule of latent TGFβ binding 
protein (LTBP). Improper extracellular localization of the latent complex can 
alter active TGFβ levels, and has been hypothesized as an explanation for 
enhanced TGFβ signaling observed in MFS. We previously reported the absence of 
LTBP-3 in matrices lacking fibrillin-1, suggesting that perturbed TGFβ signaling 
in MFS might be due to defective interaction of latent TGFβ complexes containing 
LTBP-3 with mutant fibrillin-1 microfibrils. To test this hypothesis, we 
genetically suppressed Ltbp3 expression in a mouse model of progressively severe 
MFS. Here, we present evidence that MFS mice lacking LTBP-3 have improved 
survival, essentially no aneurysms, reduced disruption and fragmentation of 
medial elastic fibers, and decreased Smad2/3 and Erk1/2 activation in their 
aortas. These data suggest that, in MFS, improper localization of latent TGFβ 
complexes composed of LTBP-3 and TGFβ contributes to aortic disease progression.