Expert consensus document: Mitochondrial function as a therapeutic target in heart failure.
Expert consensus document: Mitochondrial function as a therapeutic target in heart failure.
复制标题
DOI：
10.1038/nrcardio.2016.203
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Gheorghiade M
中科院分区：
文献类型：
--
作者：
Brown DA;Perry JB;Allen ME;Sabbah HN;Stauffer BL;Shaikh SR;Cleland JG;Colucci WS;Butler J;Voors AA;Anker SD;Pitt B;Pieske B;Filippatos G;Greene SJ;Gheorghiade M
心力衰竭是一个紧迫的全球性公共卫生问题，数百万患者患有心力衰竭恶化。尽管有所有可用的治疗方法，但这种情况的预后非常差。现有的治疗提供了症状和临床益处，但不能完全解决心肌细胞中发生的分子异常。考虑到大多数心力衰竭患者具有存活的功能障碍心肌，其中功能的改善或正常化是可能的，该缺点尤其重要。虽然心力衰竭的病理生理学是复杂的，但线粒体功能障碍似乎是直接改善心脏功能的治疗的重要靶点。线粒体异常包括线粒体电子传递链活性受损、活性氧形成增加、代谢底物利用改变、线粒体动力学异常和离子稳态改变。在这份共识声明中，介绍了心力衰竭中线粒体功能障碍机制的见解，沿着了通过靶向线粒体改善衰竭心脏功能的新兴治疗方法的概述。
Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.