Cardiac metabolism in heart failure: implications beyond ATP production.
Cardiac metabolism in heart failure: implications beyond ATP production.
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DOI：
10.1161/circresaha.113.300376
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发表时间：
2013-08-30
影响因子：
20.1
通讯作者：
Abel ED
中科院分区：
文献类型：
--
作者：
Doenst T;Nguyen TD;Abel ED
心脏有很高的ATP生产率和周转率，这是维持其连续机械工作所必需的。因此，ATP生成过程的扰动可能直接影响收缩功能。表征心力衰竭中的心脏代谢揭示了称为代谢重塑的几种代谢改变，范围从底物利用的变化到线粒体功能障碍，最终导致ATP缺乏和收缩力受损。然而，ATP耗竭不是心力衰竭期间代谢重构的唯一相关后果。通过提供细胞构建模块和信号分子，代谢途径控制细胞生长和再生等基本过程。因此，心脏代谢的改变也可能通过ATP供应以外的机制影响心力衰竭的进展。因此，我们的目的是强调心力衰竭中的代谢重构不仅导致心脏能量学受损，而且还诱导与心力衰竭发展有关的其他过程，如结构重构和氧化应激。因此，在心力衰竭中调节心脏代谢可能具有超越能量方面的显著治疗相关性。
The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect.