Failing energetics in failing hearts.
Failing energetics in failing hearts.
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DOI：
10.1007/s11886-000-0071-9
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发表时间：
2000-05-01
影响因子：
3.7
通讯作者：
Terzic, A
中科院分区：
文献类型：
--
作者：
Dzeja, P P;Redfield, M M;Terzic, A
心脏肌肉工作的持久性和旺盛性需要有效的心肌能量学。这不仅取决于足够的ATP产生，还取决于ATP向肌肉ATP酶的有效递送以及ADP和其他ATP水解副产物的快速去除。事实上，最近的证据表明，ATP产生和ATP消耗细胞位点之间的沟通缺陷是导致心力衰竭能量缺乏的主要因素。特别地，衰竭心肌的特征在于肌酸激酶、腺苷酸激酶、碳酸酐酶和糖酵解酶的催化活性降低，这些酶共同促进ATP递送并促进ADP、Pi和H+从细胞ATP酶中的去除。虽然通过腺苷酸激酶和糖酵解酶的能量转移已被认为是一种适应性机制，支持受损的肌肉能量，在失败的心肌，这些系统的总代偿潜力减少。在心肌能量信号传导的各个步骤中缺陷的逐渐积累，沿着受损的代偿机制，加速整个心脏能量系统的衰竭，最终导致心肌功能障碍。心力衰竭分子生物能量学的这些进展为改善衰竭心肌的能量平衡提供了新的视角。
The perpetual and vigorous nature of heart muscle work requires efficient myocardial energetics. This depends not only on adequate ATP production, but also on efficient delivery of ATP to muscle ATPases and rapid removal of ADP and other by-products of ATP hydrolysis. Indeed, recent evidence indicates that defects in communication between ATP-producing and ATP-consuming cellular sites are a major factor contributing to energetic deficiency in heart failure. In particular, the failing myocardium is characterized by reduced catalytic activity of creatine kinase, adenylate kinase, carbonic anhydrase, and glycolytic enzymes, which collectively facilitate ATP delivery and promote removal of ADP, Pi, and H+ from cellular ATPases. Although energy transfer through adenylate kinase and glycolytic enzymes has been recognized as an adaptive mechanism supporting compromised muscle energetics, in the failing myocardium the total compensatory potential of these systems is diminished. A gradual accumulation of defects at various steps in myocardial energetic signaling, along with compromised compensatory mechanisms, precipitates failure of the whole cardiac energetic system, ultimately contributing to myocardial dysfunction. These advances in our understanding of the molecular bioenergetics in heart failure provide a new perspective toward improving the energetic balance of the failing myocardium.