心脏能量学、力学和嘌呤核苷酸代谢的综合功能。

IF 4.2 2区 医学 Q1 PHYSIOLOGY
Rachel Lopez-Schenk, Nicole L Collins, Noah A Schenk, Daniel A Beard
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引用次数: 0

摘要

嘌呤核苷酸在心脏的能量代谢中发挥着核心作用。最基本的是,腺嘌呤核苷酸三磷酸腺苷(ATP)水解的自由能为包括肌动蛋白-肌球蛋白交桥循环在内的许多细胞过程提供了热动力。心肌中 ATP 的供应和/或需求受到干扰会导致嘌呤核苷酸合成、降解和挽救之间的平衡发生变化,从而可能影响心肌能量,进而影响心肌力学。事实上,急性心肌缺血和心力衰竭时心肌的失代偿重塑都与心肌腺嘌呤核苷酸耗竭和心肌机械功能受损有关。然而,人们对心脏病中腺嘌呤核苷酸降解与收缩功能障碍之间的机理联系的认识仍然存在差距。本文的研究范围是:(i) 回顾目前对急性缺血和慢性心脏病中嘌呤核苷酸耗竭和挽救途径的认识;(ii) 回顾心肌力学和能量学与心肌腺嘌呤核苷酸调节之间的假设关联机制;(iii) 强调治疗与这些途径相关的心肌代谢和力学功能障碍的潜在靶点。据推测,腺嘌呤核苷酸的降解、挽救和合成失衡会导致腺嘌呤核苷酸在急性缺血和与心力衰竭发展相关的慢性高需求条件下出现净损失。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 美国生理学会。Compr Physiol 14:5345-5369, 2024.
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism.

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 Physiol 14:5345-5369, 2024.

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来源期刊
CiteScore
10.50
自引率
0.00%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Comprehensive Physiology is the most authoritative and comprehensive collection of physiology information ever assembled, and uses the most powerful features of review journals and electronic reference works to cover the latest key developments in the field, through the most authoritative articles on the subjects covered. This makes Comprehensive Physiology a valued reference work on the evolving science of physiology for both researchers and clinicians. It also provides a useful teaching tool for instructors and an informative resource for medical students and other students in the life and health sciences.
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