Aortopathy in a Mouse Model of Marfan Syndrome Is Not Mediated by Altered Transforming Growth Factor β Signaling.

ABSTRACT:

Background

Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin-1 (FBN1); however, the mechanisms through which fibrillin-1 deficiency causes MFS-associated aortopathy are uncertain. Recently, attention was focused on the hypothesis that MFS-associated aortopathy is caused by increased transforming growth factor-β (TGF-β) signaling in aortic medial smooth muscle cells (SMC). However, there are many reasons to doubt that TGF-β signaling drives MFS-associated aortopathy. We used a mouse model to test whether SMC TGF-β signaling is perturbed by a fibrillin-1 variant that causes MFS and whether blockade of SMC TGF-β signaling prevents MFS-associated aortopathy.

Methods and results

MFS mice (Fbn1^C1039G/+ genotype) were genetically modified to all

SUBMITTER: Wei H 

PROVIDER: S-EPMC5523644 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature