Analysis of metabolic remodeling and mitochondrial function in heart failure

虽然线粒体在心力衰竭中起着关键作用，但在体内评估心脏线粒体功能的可行方法很少。我们验证了99mTc-MIBI的滞留对于评估体内心脏线粒体功能是有用的，并且99mTc-MIBI的洗脱增加（或滞留减少）发生在HF动物模型和HF患者中，与疾病的严重程度相关。接下来，我们研究了糖酵解酶磷酸甘油酸突变酶2 （Pgam2）持续过表达对心脏能量代谢和功能的影响。休息时葡萄糖或脂肪酸类似物的摄取和磷酸肌酸/ATP比值正常。糖酵解和乳酸最初几个步骤的代谢物水平保持不变。三羧酸（TCA）循环代谢产物水平发生改变，线粒体功能能力下降。

Although mitochondria play pivotal roles in heart failure, there are few feasible methods for cardiac assessing mitochondrial function in vivo. We validated that the retention of technetium-99m sestamibi (99mTc-MIBI) is useful for assessing cardiac mitochondrial function in vivo and that increased washout (or decreased retention) of 99mTc-MIBI occurs in an animal model of HF and patients with HF, associated with the severity of the disease.Next, we examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function. The uptake of analogs of glucose or fatty acids and the phosphocreatine/ATP ratio at rest were normal. The levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered, and the capacity of mitochondrial function was decreased.