Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Int J Mol Sci. 2021 Oct 29;22(21):11737. doi: 10.3390/ijms222111737.
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 , methionine synthase (, and methionine synthase reductase ( polymorphisms have been correlated with TAA severity in MFS patients. However, the detailed relationship between the folate-methionine cycle and MFS pathogenesis remains unclear. mice were reported to be a disease model of MFS. To study the role of the folate-methionine cycle in MFS, 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 mice. Our data showed that the and genes were suppressed in 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 -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.
胸主动脉瘤（TAA）的形成是一个多因素的过程，导致不同的临床表现和药物反应。确定马凡综合征（MFS）发病机制中的关键因素及其功能对于探索 MFS 的个性化药物治疗至关重要。亚甲基四氢叶酸还原酶、蛋氨酸合成酶（MTR）和蛋氨酸合成酶还原酶（MTRR）的多态性与 MFS 患者 TAA 的严重程度相关。然而，叶酸-蛋氨酸循环与 MFS 发病机制之间的详细关系仍不清楚。MTR 敲除（Mtr-/-）小鼠被报道为 MFS 的疾病模型。为了研究叶酸-蛋氨酸循环在 MFS 中的作用，用蛋氨酸或维生素 B 混合物（VITB）对 Mtr-/- 小鼠进行口服治疗，VITB 包含维生素 B6、B9 和 B12，持续 20 周。VITB 降低了 Mtr-/- 小鼠的心率和升主动脉周长。我们的数据表明，Mtr-/- 小鼠中的 和 基因受到抑制，而 VITB 处理将这些基因的表达恢复到正常水平。此外，VITB 恢复了经典的转化生长因子-β（TGF-β）信号通路，并促进了主动脉中层中的 介导的胶原成熟。这项研究提供了一种潜在的方法来减轻 MFS 的发病机制，可能与 MFS 患者的药物治疗具有协同作用。
