William D Watson, Per M Arvidsson, Jack J J Miller, Andrew J Lewis, Oliver J Rider
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引用次数: 0
Abstract
In health, the human heart is able to match ATP supply and demand perfectly. It requires 6 kg of ATP per day to satisfy demands of external work (mechanical force generation) and internal work (ion movements and basal metabolism). The heart is able to link supply with demand via direct responses to ADP and AMP concentrations but calcium concentrations within myocytes play a key role, signalling both inotropy, chronotropy and matched increases in ATP production. Calcium/calmodulin-dependent protein kinase (CaMKII) is a key adapter to increased workload, facilitating a greater and more rapid calcium concentration change. In the failing heart, this is dysfunctional and ATP supply is impaired. This review aims to examine the mechanisms and pathologies that link increased energy demand to this disrupted situation. We examine the roles of calcium loading, oxidative stress, mitochondrial structural abnormalities and damage-associated molecular patterns.
在健康状态下，人体心脏能够完全满足 ATP 的供需。它每天需要 6 千克的 ATP 来满足外部工作（产生机械力）和内部工作（离子运动和基础代谢）的需求。心脏能够通过对 ADP 和 AMP 浓度的直接反应将供需联系起来，但心肌细胞内的钙浓度也发挥着关键作用，它同时发出肌力、时程和 ATP 生成量匹配增加的信号。钙/钙调蛋白依赖性蛋白激酶（CaMKII）是工作负荷增加的关键适配器，可促进钙浓度发生更大、更快的变化。在衰竭的心脏中，这一功能失调，ATP 供应受损。本综述旨在研究将能量需求增加与这种紊乱状况联系起来的机制和病理。我们研究了钙负荷、氧化应激、线粒体结构异常和损伤相关分子模式的作用。
期刊介绍：
Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field.
Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients.
Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.
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