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，但目前尚无可行的方法在体内评估线粒体的功能。我们验证了99mTC-MIBI在活体心肌线粒体功能评估中的滞留是有用的，在心力衰竭和心力衰竭患者的动物模型中，99mTC-MIBI的存留增加(或减少)与疾病的严重程度有关。接下来，我们研究了糖酵解酶磷酸甘油变位酶2(PGam2)持续过表达对心脏能量代谢和功能的影响。静息状态下葡萄糖或脂肪酸类似物的摄取和磷酸肌酸/三磷酸腺苷的比率是正常的。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)循环中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.