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Identification of the metabolic remodeling profile in the early-stage of myocardial ischemia and the contributory role of mitochondrion

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posted on 23.06.2022, 10:24 authored by Jun He, Qian Liu, Jie Wang, Fangjing Xu, Yucheng Fan, Ruhua He, Ru Yan, Li Zhu

Cardiac remodeling is the primary pathological feature of chronic heart failure. Prompt inhibition of remodeling in acute coronary syndrome has been a standard procedure, but the morbidity and mortality are still high. Exploring the characteristics of ischemia in much earlier stages and identifying its biomarkers are essential for introducing novel mechanisms and therapeutic strategies. Metabolic and structural remodeling of mitochondrion is identified to play key roles in ischemic heart disease. The mitochondrial metabolic features in early ischemia have not previously been described. In the present study, we established a mouse heart in early ischemia and explored the mitochondrial metabolic profile using metabolomics analysis. We also discussed the role of mitochondrion in the global cardiac metabolism. Transmission electron microscopy revealed that mitochondrial structural injury was invoked at 8 minutes post-coronary occlusion. In total, 75 metabolites in myocardium and 26 in mitochondria were screened out. About 23% of the differentiated metabolites in mitochondria overlapped with the differentiated metabolites in myocardium; Total 81% of the perturbed metabolic pathway in mitochondria overlapped with the perturbed pathway in myocardium, and these pathways accounted for 50% of the perturbed pathway in myocardium. Purine metabolism was striking and mechanically important. In conclusion, in the early ischemia, myocardium exacerbated metabolic remodeling. Mitochondrion was a contributor to the myocardial metabolic disorder. Purine metabolism may be a potential biomarker for early ischemia diagnosis. Our study introduced a perspective for prompt identification of ischemia.

Funding

This work was supported by the National Natural Science Foundation (National Natural Science Foundation of China 81660045 to JH), Ningxia Natural Science Foundation (Natural Science Foundation of Ningxia 2020AAC02037 to JH), and First-Class Discipline Construction Founded Project of School of Clinical Medicine, Ningxia Medical University (to JH).

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