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代谢组学研究对经导管主动脉瓣置换术后严重主动脉瓣狭窄预后识别的代谢调控及潜在生物标志物

Metabolic Modulation and Potential Biomarkers of the Prognosis Identification for Severe Aortic Stenosis after TAVR by a Metabolomics Study.

作者信息

Liao Yanbiao, Liu Chang, Xiong Tianyuan, Zhao Mingyue, Zheng Wen, Feng Yuan, Li Yijian, Ou Yuanweixiang, Zhao Zhengang, Peng Yong, Wei Jiafu, Li Qiao, Meng Wei, Liu Xiaojing, Chen Mao

机构信息

Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China.

Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, China.

出版信息

Cardiol Res Pract. 2020 Oct 28;2020:3946913. doi: 10.1155/2020/3946913. eCollection 2020.

Abstract

OBJECTIVES

To investigate the metabolic profile in patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) and explore the potential biomarkers to predict prognosis after TAVR based on metabolomics.

METHODS AND RESULTS

Fifty-nine consecutive AS patients were prospectively recruited. Blood samples from the ascending aorta, coronary sinus, and peripheral vein at before and after TAVR were collected, respectively. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to analyze the metabolic profile before and after TAVR. Influential metabolites were identified by integrating the univariate test, multivariate analysis, and weighted gene coexpression network analysis (WGCNA) algorithm. PLS-DA analysis revealed a significant extremely early (within 30 minutes after TAVR) alterations of metabolites in the ascending aorta, coronary sinus, and peripheral vein. The early (within 7 days after TAVR) changed metabolites in the peripheral vein were involved in purine metabolism, primary bile acid biosynthesis, glycerolipid metabolism, amino sugar and nucleotide sugar metabolism, one carbon pool by folate and alanine, and the aspartate and glutamate metabolism pathway. We used volcano plots to find that the cardiac-specific changed metabolites were enriched to the sphingolipid metabolism pathway after TAVR. Besides, WGCNA algorithm was performed to reveal that arginine and proline metabolites could reflect left ventricle regression to some extent.

CONCLUSION

This is the first study to reveal systemic and cardiac metabolites changed significantly in patients with AS after TAVR. Some altered metabolites involved in the arginine and proline metabolism pathway in the peripheral vein could predict left ventricle regression, which merited further study.

摘要

目的

研究经导管主动脉瓣置换术(TAVR)后主动脉瓣狭窄(AS)患者的代谢谱,并基于代谢组学探索预测TAVR后预后的潜在生物标志物。

方法与结果

前瞻性招募了59例连续的AS患者。分别采集TAVR前后升主动脉、冠状窦和外周静脉的血样。采用液相色谱 - 质谱联用和气相色谱 - 质谱联用技术分析TAVR前后的代谢谱。通过整合单变量检验、多变量分析和加权基因共表达网络分析(WGCNA)算法鉴定有影响的代谢物。PLS - DA分析显示,TAVR后极早期(TAVR后30分钟内)升主动脉、冠状窦和外周静脉中的代谢物有显著变化。外周静脉中早期(TAVR后7天内)变化的代谢物涉及嘌呤代谢、初级胆汁酸生物合成、甘油olipid代谢、氨基糖和核苷酸糖代谢、叶酸和丙氨酸的一碳池以及天冬氨酸和谷氨酸代谢途径。我们使用火山图发现,TAVR后心脏特异性变化的代谢物富集到鞘脂代谢途径。此外,进行WGCNA算法以揭示精氨酸和脯氨酸代谢物在一定程度上可以反映左心室的恢复。

结论

这是第一项揭示TAVR后AS患者全身和心脏代谢物发生显著变化的研究。外周静脉中一些参与精氨酸和脯氨酸代谢途径的代谢物变化可能预测左心室恢复,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ca7/7649585/4cfbdc973240/CRP2020-3946913.001.jpg

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