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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Autores principales:	Tzu-Heng Huang, Hsiao-Huang Chang, Yu-Ru Guo, Wei-Chiao Chang, Yi-Fan Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Marfan syndrome fibrillin 1 mutation thoracic aortic aneurysm (TAA) thoracic aortic dissection (TAD) vitamin B folate-methionine cycle Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4268512a53e44801b61c971f10953ed5
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spelling	oai:doaj.org-article:4268512a53e44801b61c971f10953ed52021-11-11T17:11:45ZVitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway10.3390/ijms2221117371422-00671661-6596https://doaj.org/article/4268512a53e44801b61c971f10953ed52021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11737https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Thoracic 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.Tzu-Heng HuangHsiao-Huang ChangYu-Ru GuoWei-Chiao ChangYi-Fan ChenMDPI AGarticleMarfan syndromefibrillin 1 mutationthoracic aortic aneurysm (TAA)thoracic aortic dissection (TAD)vitamin Bfolate-methionine cycleBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11737, p 11737 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Marfan syndrome fibrillin 1 mutation thoracic aortic aneurysm (TAA) thoracic aortic dissection (TAD) vitamin B folate-methionine cycle Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Marfan syndrome fibrillin 1 mutation thoracic aortic aneurysm (TAA) thoracic aortic dissection (TAD) vitamin B folate-methionine cycle Biology (General) QH301-705.5 Chemistry QD1-999 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
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.
format	article
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
title	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_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_sort	vitamin b mitigates thoracic aortic dilation in marfan syndrome mice by restoring the canonical tgf-β pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4268512a53e44801b61c971f10953ed5
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Vitamin B Mitigates Thoracic Aortic Dilation in Marfan Syndrome Mice by Restoring the Canonical TGF-β Pathway

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