Department of Human Nutrition, Foods, and Exercise, Virginia Tech, 1035 Integrated Life Sciences Building, 1981 Kraft Drive, Blacksburg, Virginia 24060, USA.
Division of Cardiovascular Medicine, Department of Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202, USA.
Nat Rev Cardiol. 2017 Apr;14(4):238-250. doi: 10.1038/nrcardio.2016.203. Epub 2016 Dec 22.
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.
心力衰竭是一个全球性的紧迫公共卫生问题，数以百万计的心力衰竭患者病情正在恶化。尽管有所有可用的疗法，但这种情况的预后非常差。现有的治疗方法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。鉴于大多数心力衰竭患者都有存活但功能失调的心肌，改善或恢复其功能是有可能的，这种缺陷尤其重要。尽管心力衰竭的病理生理学很复杂，但线粒体功能障碍似乎是一种重要的治疗靶点，可以直接改善心脏功能。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、代谢底物利用发生转移、线粒体动力学异常以及离子内稳态改变。在这份共识声明中，介绍了心力衰竭中线粒体功能障碍的机制，并概述了新兴的治疗方法，这些方法有可能通过靶向线粒体来改善衰竭心脏的功能。
