Hua Tong, Bao Qiankun, He Xue, Cai Wenbin, He Jinlong
Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Front Physiol. 2021 Mar 12;12:663480. doi: 10.3389/fphys.2021.663480. eCollection 2021.
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.
鞘脂代谢异常会导致心脏病理生理改变。新出现的证据表明，在心肌梗死后（MI）的炎症阶段，神经酰胺水平升高作为一种生物标志物，与心脏功能障碍有关。然而，MI后修复期鞘脂谱的变化仍未完全了解。我们使用导致MI的左前降支结扎小鼠模型，进行代谢组学研究，以评估MI后修复期血浆和心肌鞘脂谱的变化。总共检测到193种鞘脂代谢物。MI损伤后，心肌鞘脂而非血浆鞘脂出现显著变化。MI后积累的1-磷酸神经酰胺对两组间鞘脂谱的差异有很大影响。同样，将神经酰胺磷酸化生成1-磷酸神经酰胺的神经酰胺激酶的表达在MI损伤后的心脏组织中上调。我们的研究结果揭示了MI后修复期鞘脂代谢的变化，并突出了神经酰胺激酶/1-磷酸神经酰胺在缺血性心脏病中的潜在作用。
