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Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models

Violette Deleeuw (UGent) , Eric Carlson, Marjolijn Renard (UGent) , Keith D. Zientek, Phillip A. Wilmarth, Ashok P. Reddy, Elise C. Manalo, Sara F. Tufa, Douglas R. Keene, Margie Olbinado, et al.
(2023) MATRIX BIOLOGY. 123. p.17-33
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Abstract
Although 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.
Keywords
Molecular Biology, Mouse models, TGF beta signaling, Aortic aneurysm and dissection, Marfan syndrome, Fibrillin

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MLA
Deleeuw, Violette, et al. “Unraveling the Role of TGFβ Signaling in Thoracic Aortic Aneurysm and Dissection Using Fbn1 Mutant Mouse Models.” MATRIX BIOLOGY, vol. 123, Elsevier BV, 2023, pp. 17–33, doi:10.1016/j.matbio.2023.09.001.
APA
Deleeuw, V., Carlson, E., Renard, M., Zientek, K. D., Wilmarth, P. A., Reddy, A. P., … Sakai, L. Y. (2023). Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models. MATRIX BIOLOGY, 123, 17–33. https://doi.org/10.1016/j.matbio.2023.09.001
Chicago author-date
Deleeuw, Violette, Eric Carlson, Marjolijn Renard, Keith D. Zientek, Phillip A. Wilmarth, Ashok P. Reddy, Elise C. Manalo, et al. 2023. “Unraveling the Role of TGFβ Signaling in Thoracic Aortic Aneurysm and Dissection Using Fbn1 Mutant Mouse Models.” MATRIX BIOLOGY 123: 17–33. https://doi.org/10.1016/j.matbio.2023.09.001.
Chicago author-date (all authors)
Deleeuw, Violette, 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 Muiño Mosquera, Patrick Sips, Julie De Backer, and Lynn Y. Sakai. 2023. “Unraveling the Role of TGFβ Signaling in Thoracic Aortic Aneurysm and Dissection Using Fbn1 Mutant Mouse Models.” MATRIX BIOLOGY 123: 17–33. doi:10.1016/j.matbio.2023.09.001.
Vancouver
1.
Deleeuw V, Carlson E, Renard M, Zientek KD, Wilmarth PA, Reddy AP, et al. Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models. MATRIX BIOLOGY. 2023;123:17–33.
IEEE
[1]
V. Deleeuw et al., “Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models,” MATRIX BIOLOGY, vol. 123, pp. 17–33, 2023.
@article{01H9THS11KG3ECMPXJY4EN7PB8,
  abstract     = {{Although 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.}},
  author       = {{Deleeuw, Violette and Carlson, Eric and Renard, Marjolijn and Zientek, Keith D. and Wilmarth, Phillip A. and Reddy, Ashok P. and Manalo, Elise C. and Tufa, Sara F. and Keene, Douglas R. and Olbinado, Margie and Stampanoni, Marco and Kanki, Sachiko and Yanagisawa, Hiromi and Muiño Mosquera, Laura and Sips, Patrick and De Backer, Julie and Sakai, Lynn Y.}},
  issn         = {{0945-053X}},
  journal      = {{MATRIX BIOLOGY}},
  keywords     = {{Molecular Biology,Mouse models,TGF beta signaling,Aortic aneurysm and dissection,Marfan syndrome,Fibrillin}},
  language     = {{eng}},
  pages        = {{17--33}},
  publisher    = {{Elsevier BV}},
  title        = {{Unraveling the role of TGFβ signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models}},
  url          = {{http://doi.org/10.1016/j.matbio.2023.09.001}},
  volume       = {{123}},
  year         = {{2023}},
}
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