Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance
Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance
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DOI：
10.1016/j.jchf.2016.03.011
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发表时间：
2016-08-01
影响因子：
13
通讯作者：
Kitzman, Dalane W.
中科院分区：
文献类型：
--
作者：
Molina, Anthony J. A.;Bharadwaj, Manish S.;Kitzman, Dalane W.
本研究的目的是检测射血分数保留性心力衰竭（HFpEF）患者的骨骼肌线粒体含量、氧化能力和关键线粒体动力学蛋白的表达，背景多条证据表明，严重降低的峰值运动摄氧量HFpEF老年患者的峰值VO2与骨骼肌氧利用异常有关。线粒体是骨骼肌代谢的关键调节器;方法检测老年HFpEF患者（n = 20）和年龄匹配的健康对照者（n = 17）股外侧肌骨骼肌柠檬酸合酶活性、孔蛋白和线粒体融合调节因子的表达。在HFpEF患者中，通过孔蛋白表达评估的线粒体含量降低46%（p = 0.01），柠檬酸合酶活性降低29%（p = 0.01），Mfn2（线粒体融合蛋白2）表达降低54%（p <0.001）。孔蛋白的表达与峰值VO2和6分钟步行距离显著正相关（分别为r = 0.48，p = 0.003和r = 0.33，p = 0.05）。Mfn2的表达也与峰值VO2和6分钟步行距离呈显著正相关（分别为r = 0.40，p = 0.02和r = 0.37，p = 0.03）。结论这些结果表明，骨骼肌氧化能力，线粒体含量和线粒体融合在老年HFpEF患者中异常，可能是导致他们严重运动不耐受的原因。(C)2016年由美国心脏病学会基金会。
OBJECTIVES The aim of this study was to examine skeletal muscle mitochondria content, oxidative capacity, and the expression of key mitochondrial dynamics proteins in patients with heart failure with preserved ejection fraction (HFpEF), as well as to determine potential relationships with measures of exercise performance.BACKGROUND Multiple lines of evidence indicate that severely reduced peak exercise oxygen uptake (peak VO2) in older patients with HFpEF is related to abnormal skeletal muscle oxygen utilization. Mitochondria are key regulators of skeletal muscle metabolism; however, little is known about how these organelles are affected in HFpEF.METHODS Both vastus lateralis skeletal muscle citrate synthase activity and the expression of porin and regulators of mitochondrial fusion were examined in older patients with HFpEF (n = 20) and healthy, age-matched control subjects (n = 17).RESULTS Compared with age-matched healthy control subjects, mitochondrial content assessed by porin expression was 46% lower (p = 0.01), citrate synthase activity was 29% lower (p = 0.01), and Mfn2 (mitofusin 2) expression was 54% lower (p < 0.001) in patients with HFpEF. Expression of porin was significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.48, p = 0.003 and r = 0.33, p = 0.05, respectively). Expression of Mfn2 was also significantly positively correlated with both peak VO2 and 6-min walk distance (r = 0.40, p = 0.02 and r = 0.37, p = 0.03 respectively).CONCLUSIONS These findings suggest that skeletal muscle oxidative capacity, mitochondrial content, and mitochondrial fusion are abnormal in older patients with HFpEF and might contribute to their severe exercise intolerance. (C) 2016 by the American College of Cardiology Foundation.