Lipidomics Revealed Alteration of Sphingolipid Metabolism During the Reparative Phase After Myocardial Infarction Injury.

Lipidomics Revealed Alteration of Sphingolipid Metabolism During the Reparative Phase After Myocardial Infarction Injury.
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脂质组学揭示心肌梗塞损伤后修复阶段鞘脂代谢的变化

DOI:
10.3389/fphys.2021.663480
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发表时间:
2021
影响因子:
4
通讯作者:
He J
He J
中科院分区:
医学2区
文献类型:
--
作者:
Hua T;Bao Q;He X;Cai W;He J

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异常鞘脂代谢有助于心脏病理生理学。新出现的证据发现,在心肌梗死(MI)后的炎症阶段,神经酰胺水平升高可作为一种生物标志物,并与心功能不全相关。然而,在MI后的修复阶段鞘脂谱的变化仍然没有完全理解。使用左前降支结扎导致MI的小鼠模型,我们进行了代谢组学研究,以评估MI后修复阶段血浆和心肌鞘脂谱的变化。共检测到193种鞘脂代谢产物。心肌损伤后,心肌鞘脂有明显变化,而血浆鞘脂无明显变化。神经酰胺-1-磷酸盐,这是积累MI后,高度促成组间鞘脂谱的差异。因此,心肌梗死后心肌组织中神经酰胺激酶的表达上调,神经酰胺激酶磷酸化神经酰胺生成神经酰胺-1-磷酸。我们的研究结果揭示了心肌梗死后修复阶段鞘脂代谢的改变,并强调了神经酰胺激酶/神经酰胺-1-磷酸在缺血性心脏病中的潜在作用。
Aberrant sphingolipid metabolism contributes to cardiac pathophysiology. Emerging evidence found that an increased level of ceramide during the inflammatory phase of post-myocardial infarction (MI) served as a biomarker and was associated with cardiac dysfunction. However, the alternation of the sphingolipid profile during the reparative phase after MI is still not fully understood. Using a mouse model of the left anterior descending ligation that leads to MI, we performed metabolomics studies to assess the alternations of both plasma and myocardial sphingolipid profiles during the reparative phase post-MI. A total number of 193 sphingolipid metabolites were detected. Myocardial sphingolipids but not plasma sphingolipids showed marked change after MI injury. Ceramide-1-phosphates, which were accumulated after MI, contributed highly to the difference in sphingolipid profiles between groups. Consistently, the expression of ceramide kinase, which phosphorylates ceramides to generate ceramide-1-phosphates, was upregulated in heart tissue after MI injury. Our findings revealed the altering sphingolipid metabolism during the reparative phase post-MI and highlighted the potential role of ceramide kinase/ceramide-1-phosphate in ischemic heart disease.
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