Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism.
Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism.
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心脏能量学、力学和嘌呤核苷酸代谢的综合功能。
DOI：
10.1002/cphy.c230011
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发表时间：
2023
影响因子：
5.8
通讯作者：
Beard,DanielA
中科院分区：
文献类型：
--
作者：
Lopez-Schenk,Rachel;Collins,NicoleL;Schenk,NoahA;Beard,DanielA
嘌呤核苷酸在心脏的能量代谢中起核心作用。最根本的是，腺嘌呤核苷酸三磷酸腺苷（ATP）水解的自由能为许多细胞过程提供了热力学驱动力，包括肌动蛋白-肌球蛋白交联循环。心肌中ATP供应和/或需求的扰动导致嘌呤核苷酸合成、降解和补救之间的稳态平衡发生变化，可能影响心肌能量学，从而影响心肌力学。事实上，急性心肌缺血和心力衰竭时心肌的失代偿性重构都与心肌腺嘌呤核苷酸的耗竭和心肌机械功能受损有关。然而，在心脏病中腺嘌呤核苷酸降解和收缩功能障碍之间的机械联系的理解仍然存在差距。这篇文章的范围是：（一）审查目前的知识嘌呤核苷酸消耗和补救途径在急性缺血和慢性心脏病;（二）审查假设的机制，心肌力学和能量与心肌腺嘌呤核苷酸调节;和（三）突出潜在的目标，治疗心肌代谢和机械功能障碍与这些途径。据推测，腺嘌呤核苷酸的降解、挽救和合成的不平衡导致急性缺血和慢性高需求条件下腺嘌呤核苷酸的净损失，与心力衰竭的发展相关。这种腺嘌呤核苷酸水平的降低导致心肌ATP减少和心肌无机磷酸盐增加。这两种变化都有可能直接影响细胞水平的张力发展和机械功。© 2024 American Physiological Society.Compr Physiol 14：5345 - 5369，2024.
Purine nucleotides play central roles in energy metabolism in the heart. Most fundamentally, the free energy of hydrolysis of the adenine nucleotide adenosine triphosphate (ATP) provides the thermodynamic driving force for numerous cellular processes including the actin‐myosin crossbridge cycle. Perturbations to ATP supply and/or demand in the myocardium lead to changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage, potentially affecting myocardial energetics and, consequently, myocardial mechanics. Indeed, both acute myocardial ischemia and decompensatory remodeling of the myocardium in heart failure are associated with depletion of myocardial adenine nucleotides and with impaired myocardial mechanical function. Yet there remain gaps in the understanding of mechanistic links between adenine nucleotide degradation and contractile dysfunction in heart disease. The scope of this article is to: (i) review current knowledge of the pathways of purine nucleotide depletion and salvage in acute ischemia and in chronic heart disease; (ii) review hypothesized mechanisms linking myocardial mechanics and energetics with myocardial adenine nucleotide regulation; and (iii) highlight potential targets for treating myocardial metabolic and mechanical dysfunction associated with these pathways. It is hypothesized that an imbalance in the degradation, salvage, and synthesis of adenine nucleotides leads to a net loss of adenine nucleotides in both acute ischemia and under chronic high‐demand conditions associated with the development of heart failure. This reduction in adenine nucleotide levels results in reduced myocardial ATP and increased myocardial inorganic phosphate. Both of these changes have the potential to directly impact tension development and mechanical work at the cellular level. © 2024 American Physiological Society.Compr Physiol14:5345‐5369, 2024.