Related Experiment Video
Updated: Jul 30, 2026
Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta
Published on: September 12, 2017
Proximal aortic aneurysms in mice underexpressing transforming growth factor-β1
Masao Kakoki1, John R Hagaman2, Masahiko Terajima3
1Department of Physiology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga district, Mibu, Tochigi 321-0293, Japan.
Abstract:
In humans, loss-of-function mutations in multiple component genes of transforming growth factor (TGF)-β signaling have been demonstrated to cause proximal aortic aneurysms. However, association of human variants in the prototype ligand TGFB1 with thoracic aortic aneurysms have not been reported to date. To delineate the consequences of genetically altered Tgfb1 expression on aortic phenotype in mammals, we studied aortic phenotype in mice with loss-of-functions or gain-of-function mutations in Tgfb1 (Tgfb1L/L and Tgfb1H/H). Tgfb1L/L mice spontaneously developed proximal aortic aneurysms and had markedly shortened lifespans as compared with wildtype, whereas Tgfb1H/Hmice did not develop aortic aneurysms and had comparable lifespans with wildtype. Aortic levels of collagen and elastin stable crosslinks, and the expression of their associated enzymes in Tgfb1L/L mice were significantly less than those in wildtype. These results suggest that TGF-β1 is protective against aortic aneurysms at least partly via increasing the cross-linking of collagen and elastin.
Insights
Transforming growth factor-beta 1 (TGF-β1) loss-of-function mutations cause aortic aneurysms in mice by reducing collagen and elastin cross-linking. This suggests TGF-β1 is protective against thoracic aortic aneurysms.
Area of Science:
- Cardiovascular Biology
- Genetics
- Molecular Biology
Background:
- Transforming growth factor (TGF)-β signaling pathway mutations are linked to aortic aneurysms.
- The role of the prototype ligand TGFB1 in thoracic aortic aneurysms remains uncharacterized in humans.
Purpose of the Study:
- To investigate the impact of altered TGFB1 gene expression on aortic aneurysm development in a mammalian model.
- To determine if TGF-β1 plays a protective role in aortic integrity.
Main Methods:
- Studied aortic phenotypes in mice with genetic modifications for TGFB1 loss-of-function (Tgfb1L/L) and gain-of-function (Tgfb1H/H).
- Compared lifespan and aortic characteristics of mutant mice with wildtype controls.
- Quantified aortic levels of collagen and elastin stable crosslinks and associated enzyme expression.
Main Results:
- Tgfb1L/L mice developed spontaneous proximal aortic aneurysms and exhibited reduced lifespans compared to wildtype.
- Tgfb1H/H mice did not develop aortic aneurysms and had comparable lifespans to wildtype.
- Aortic collagen and elastin cross-linking, along with related enzyme expression, were significantly decreased in Tgfb1L/L mice.
Conclusions:
- Loss-of-function mutations in TGFB1 are sufficient to cause aortic aneurysms in mice.
- TGF-β1 appears to be protective against aortic aneurysms, at least partially by enhancing collagen and elastin cross-linking.
- These findings highlight TGF-β1's critical role in maintaining aortic wall integrity.
More Related Videos
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:16TGF - β Signaling Pathway