In a new research article titled Unraveling the Role of TGFβ Signaling in Thoracic Aortic Aneurysm and Dissection Using Fbn1 Mutant Mouse Models has been published in Matrix Biology and co-authored by Prof. Julie De BACKER and Dr Laura MUIÑO MOSQUERA, members of the Heritable Thoracic Aortic Diseases Working Group.
This article delves into the intricate relationship between abnormal TGFβ signaling and heritable forms of thoracic aortic aneurysms and dissections, including Marfan syndrome. The study, employing a mouse genetic approach and quantitative isobaric labeling proteomics, aims to shed light on the precise role of TGFβ signaling in the progression of aortic diseases.
The three Fbn1 mutant mouse models utilized in the study represent a spectrum of aortic diseases, ranging from microdissection (without an aneurysm) to aneurysm (without rupture) and, finally, aneurysm and rupture. The results offer a nuanced understanding of the connection between TGFβ signaling and the various stages of thoracic aortic disease.
Key findings from the study revealed that reduced TGFβ signaling and increased mast cell proteases were associated with microdissection. Conversely, aneurysm development was linked to an increased abundance of extracellular matrix proteins, potentially serving as indicators of positive TGFβ signaling. The most notable discovery was the marked reductions in collagens and fibrillins, coupled with heightened TGFβ signaling, in cases of aortic rupture. The data presented in this paper indicate that TGFβ signaling plays context-dependent roles in the pathogenesis of thoracic aortic diseases.
For those eager to explore the details of this groundbreaking study, the full publication can be accessed here.
Reference: Deleeuw V, Carlson E, Renard M, Zientek KD, Wilmarth PA, Reddy AP, Manalo EC, Tufa SF, Keene DR, Olbinado M, Stampanoni M, Kanki S, Yanagisawa H, Mosquera LM, Sips P, De Backer J, Sakai LY. Unraveling the Role of TGFβ 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. Epub ahead of print. PMID: 37683955.