Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway
Thoracic aortic aneurysm (TAA) formation is a multifactorial process that results in diverse clinical manifestations and drug responses. Identifying the critical factors and their functions in Marfan syndrome (MFS) pathogenesis is important for exploring personalized medicine for MFS. Methylenetetra...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Tzu-Heng Huang Hsiao-Huang Chang Yu-Ru Guo Wei-Chiao Chang Yi-Fan Chen |
| author_facet | Tzu-Heng Huang Hsiao-Huang Chang Yu-Ru Guo Wei-Chiao Chang Yi-Fan Chen |
| author_sort | Tzu-Heng Huang |
| collection | DOAJ |
| description | Thoracic aortic aneurysm (TAA) formation is a multifactorial process that results in diverse clinical manifestations and drug responses. Identifying the critical factors and their functions in Marfan syndrome (MFS) pathogenesis is important for exploring personalized medicine for MFS. Methylenetetrahydrofolate reductase <i>(MTHFR)</i>, methionine synthase (<i>MTR)</i>, and methionine synthase reductase (<i>MTRR)</i> polymorphisms have been correlated with TAA severity in MFS patients. However, the detailed relationship between the folate-methionine cycle and MFS pathogenesis remains unclear. <i>Fbn1</i><sup>C1039G/+</sup> mice were reported to be a disease model of MFS. To study the role of the folate-methionine cycle in MFS, <i>Fbn1</i><sup>C1039G/+</sup> mice were treated orally with methionine or vitamin B mixture (VITB), including vitamins B6, B9, and B12, for 20 weeks. VITB reduced the heart rate and circumference of the ascending aorta in <i>Fbn1</i><sup>C1039G/+</sup> mice. Our data showed that the <i>Mtr</i> and <i>Smad4</i> genes were suppressed in <i>Fbn1</i><sup>C1039G/+</sup> mice, while VITB treatment restored the expression of these genes to normal levels. Additionally, VITB restored canonical transforming-growth factor β (TGF-β) signaling and promoted <i>Loxl1</i>-mediated collagen maturation in aortic media. This study provides a potential method to attenuate the pathogenesis of MFS that may have a synergistic effect with drug treatments for MFS patients. |
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| spelling | doaj.art-4268512a53e44801b61c971f10953ed52023-11-22T20:57:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211173710.3390/ijms222111737Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β PathwayTzu-Heng Huang0Hsiao-Huang Chang1Yu-Ru Guo2Wei-Chiao Chang3Yi-Fan Chen4Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanDivision of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanMaster Program in Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanMaster Program in Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanThoracic aortic aneurysm (TAA) formation is a multifactorial process that results in diverse clinical manifestations and drug responses. Identifying the critical factors and their functions in Marfan syndrome (MFS) pathogenesis is important for exploring personalized medicine for MFS. Methylenetetrahydrofolate reductase <i>(MTHFR)</i>, methionine synthase (<i>MTR)</i>, and methionine synthase reductase (<i>MTRR)</i> polymorphisms have been correlated with TAA severity in MFS patients. However, the detailed relationship between the folate-methionine cycle and MFS pathogenesis remains unclear. <i>Fbn1</i><sup>C1039G/+</sup> mice were reported to be a disease model of MFS. To study the role of the folate-methionine cycle in MFS, <i>Fbn1</i><sup>C1039G/+</sup> mice were treated orally with methionine or vitamin B mixture (VITB), including vitamins B6, B9, and B12, for 20 weeks. VITB reduced the heart rate and circumference of the ascending aorta in <i>Fbn1</i><sup>C1039G/+</sup> mice. Our data showed that the <i>Mtr</i> and <i>Smad4</i> genes were suppressed in <i>Fbn1</i><sup>C1039G/+</sup> mice, while VITB treatment restored the expression of these genes to normal levels. Additionally, VITB restored canonical transforming-growth factor β (TGF-β) signaling and promoted <i>Loxl1</i>-mediated collagen maturation in aortic media. This study provides a potential method to attenuate the pathogenesis of MFS that may have a synergistic effect with drug treatments for MFS patients.https://www.mdpi.com/1422-0067/22/21/11737Marfan syndromefibrillin 1 mutationthoracic aortic aneurysm (TAA)thoracic aortic dissection (TAD)vitamin Bfolate-methionine cycle |
| spellingShingle | Tzu-Heng Huang Hsiao-Huang Chang Yu-Ru Guo Wei-Chiao Chang Yi-Fan Chen Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway International Journal of Molecular Sciences Marfan syndrome fibrillin 1 mutation thoracic aortic aneurysm (TAA) thoracic aortic dissection (TAD) vitamin B folate-methionine cycle |
| title | Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway |
| title_full | Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway |
| title_fullStr | Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway |
| title_full_unstemmed | Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway |
| title_short | Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway |
| title_sort | vitamin b mitigates thoracic aortic dilation in marfan syndrome mice by restoring the canonical tgf β pathway |
| topic | Marfan syndrome fibrillin 1 mutation thoracic aortic aneurysm (TAA) thoracic aortic dissection (TAD) vitamin B folate-methionine cycle |
| url | https://www.mdpi.com/1422-0067/22/21/11737 |
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