Unraveling the Role of TGF β Signaling in Thoracic Aortic Aneurysm and Dissection Using Fbn1 Mutant Mouse Models

Matrix Biol. 2023 Sep 6:S0945-053X(23)00095-1. doi: 10.1016/j.matbio.2023.09.001. Online ahead of print.ABSTRACTAlthough abnormal TGFβ signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, its precise role in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to elucidate the role of TGFβ signaling in three Fbn1 mutant mouse models representing a range of aortic disease from microdissection (without aneurysm) to aneurysm (without rupture) to aneurysm and rupture. Results indicated that reduced TGFβ signaling and increased mast cell proteases were associated with microdissection. In contrast, increased abundance of extracellular matrix proteins, which could be reporters for positive TGFβ signaling, were associated with aneurysm. Marked reductions in collagens and fibrillins, and increased TGFβ signaling, were associated with aortic rupture. Our data indicate that TGFβ signaling performs context-dependent roles in the pathogenesis of thoracic aortic disease.PMID:37683955 | DOI:10.1016/j.matbio.2023.09.001

Source: Matrix Biology - September 8, 2023 Category: Molecular Biology Authors: Violette Deleeuw Eric Carlson Marjolijn Renard Keith D Zientek Phillip A Wilmarth Ashok P Reddy Elise C Manalo Sara F Tufa Douglas R Keene Margie Olbinado Marco Stampanoni Sachiko Kanki Hiromi Yanagisawa Laura Mui ño Mosquera Patrick Sips Julie De Backer Source Type: research