Mitochondrial Dysfunction in Heart Failure With Preserved Ejection Fraction
Mitochondrial Dysfunction in Heart Failure With Preserved Ejection Fraction
复制标题
射血分数保留的心力衰竭患者线粒体功能障碍
DOI：
10.1161/circulationaha.118.036259
复制
发表时间：
2019-03-12
期刊：
影响因子：
37.8
通讯作者：
Chirinos, Julio A.
中科院分区：
文献类型：
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作者：
Kumar, Anupam A.;Kelly, Daniel P.;Chirinos, Julio A.
射血分数保留性心力衰竭（HFpEF）是一种复杂的综合征，其病理生理学异质性日益受到重视。运动不耐受是HFpEF的标志，似乎是由动脉树和骨骼肌中的心脏和外周异常引起的。线粒体异常可显著导致HFpEF中氧利用受损和由此产生的运动不耐受。我们回顾了这个细胞器的复杂生物学的关键方面，线粒体功能的临床相关性，目前可用于评估人类线粒体功能的方法，以及支持线粒体功能障碍在HFpEF病理生理学中作用的证据。我们还讨论了线粒体功能作为治疗靶点的作用，设计早期临床试验的一些关键考虑因素，这些试验使用专门针对线粒体功能的药物来改善HFpEF患者的症状，以及正在进行的HFpEF线粒体药物试验。
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with an increasingly recognized heterogeneity in pathophysiology. Exercise intolerance is the hallmark of HFpEF and appears to be caused by both cardiac and peripheral abnormalities in the arterial tree and skeletal muscle. Mitochondrial abnormalities can significantly contribute to impaired oxygen utilization and the resulting exercise intolerance in HFpEF. We review key aspects of the complex biology of this organelle, the clinical relevance of mitochondrial function, the methods that are currently available to assess mitochondrial function in humans, and the evidence supporting a role for mitochondrial dysfunction in the pathophysiology of HFpEF. We also discuss the role of mitochondrial function as a therapeutic target, some key considerations for the design of early-phase clinical trials using agents that specifically target mitochondrial function to improve symptoms in patients with HFpEF, and ongoing trials with mitochondrial agents in HFpEF.