Key result
Early myocardial ischemia induced by coronary occlusion in mice resulted in mitochondrial structural injury at 8 minutes and significant metabolic remodeling, notably in purine metabolism.
Why the study?
Mitochondrial metabolic and structural remodeling plays key roles in ischemic heart disease, but the mitochondrial metabolic features in early ischemia have not previously been described.
Early myocardial ischemia induces rapid mitochondrial structural injury and metabolic remodeling, particularly in purine metabolism, which may serve as a potential biomarker for early diagnosis.
Hypothesis-generating for purine metabolites as early ischemia biomarkers; clinical validation needed before diagnostic use.
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.
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He et al. (2022) studied early myocardial ischemia. coronary occlusion was evaluated on metabolic profile and structural injury. Early myocardial ischemia induced by coronary occlusion in mice resulted in mitochondrial structural injury at 8 minutes and significant metabolic remodeling, notably in purine metabolism.
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