Wang Qian, An Jun, Zhou Wei, Zhang Yujing, Huang Jiang, Liao Geping, Wang Mingzhe, Xia Lingbo, Le Aiping, Zhu Jianbing
Department of Transfusion Medicine, Key Laboratory of Jiangxi Province for Transfusion Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Nutr Metab (Lond). 2024 Aug 19;21(1):67. doi: 10.1186/s12986-024-00837-5.
Methionine, an indispensable amino acid crucial for dietary balance, intricately governs metabolic pathways. Disruption in its equilibrium has the potential to heighten homocysteine levels in both plasma and tissues, posing a conceivable risk of inducing inflammation and detriment to the integrity of vascular endothelial cells. The intricate interplay between methionine metabolism, with a specific focus on S-adenosyl-L-methionine (SAM), and the onset of thoracic aortic dissection (TAD) remains enigmatic despite acknowledging the pivotal role of inflammation in this vascular condition. In an established murine model induced by β-aminopropionitrile monofumarate (BAPN), we delved into the repercussions of supplementing with S-adenosyl-L-methionine (SAM) on the progression of TAD. Our observations uncovered a noteworthy improvement in aortic dissection and rupture rates, accompanied by a marked reduction in mortality upon SAM supplementation. Notably, SAM supplementation exhibited a considerable protective effect against BAPN-induced degradation of elastin and the extracellular matrix. Furthermore, SAM supplementation demonstrated a robust inhibitory influence on the infiltration of immune cells, particularly neutrophils and macrophages. It also manifested a notable reduction in the inflammatory polarization of macrophages, evident through diminished accumulation of MHC-II macrophages and reduced expression of inflammatory cytokines such as IL1β and TNFα in macrophages. Simultaneously, SAM supplementation exerted a suppressive effect on the activation of CD4 + and CD8 + T cells within the aorta. This was evidenced by an elevated proportion of CD44- CD62L + naïve T cells and a concurrent decrease in CD44 + CD62L- effector T cells. In summary, our findings strongly suggest that the supplementation of SAM exhibits remarkable efficacy in alleviating BAPN-induced aortic inflammation, consequently impeding the progression of thoracic aortic dissection.
蛋氨酸是饮食平衡中不可或缺的氨基酸，对代谢途径有着复杂的调控作用。其平衡的破坏有可能提高血浆和组织中的同型半胱氨酸水平，从而可能引发炎症并损害血管内皮细胞的完整性。尽管认识到炎症在这种血管疾病中的关键作用，但蛋氨酸代谢（特别是S-腺苷-L-蛋氨酸（SAM））与胸主动脉夹层（TAD）发病之间的复杂相互作用仍不清楚。在由单富马酸β-氨基丙腈（BAPN）诱导的既定小鼠模型中，我们深入研究了补充S-腺苷-L-蛋氨酸（SAM）对TAD进展的影响。我们的观察结果发现，补充SAM后，主动脉夹层和破裂率有显著改善，死亡率也显著降低。值得注意的是，补充SAM对BAPN诱导的弹性蛋白和细胞外基质降解具有相当大的保护作用。此外，补充SAM对免疫细胞的浸润，特别是中性粒细胞和巨噬细胞，表现出强大的抑制作用。它还使巨噬细胞的炎症极化显著降低，这通过MHC-II巨噬细胞积累减少以及巨噬细胞中IL1β和TNFα等炎症细胞因子表达降低得以体现。同时，补充SAM对主动脉内CD4 +和CD8 + T细胞的激活具有抑制作用。这表现为CD44-CD62L +幼稚T细胞比例升高，同时CD44 + CD62L-效应T细胞减少。总之，我们的研究结果强烈表明，补充SAM在减轻BAPN诱导的主动脉炎症方面具有显著效果，从而阻碍胸主动脉夹层的进展。
