Mitochondrial Morphology, Dynamics, and Function in Human Pressure Overload or Ischemic Heart Disease With Preserved or Reduced Ejection Fraction
Mitochondrial Morphology, Dynamics, and Function in Human Pressure Overload or Ischemic Heart Disease With Preserved or Reduced Ejection Fraction
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DOI：
10.1161/circheartfailure.118.005131
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发表时间：
2019-02-01
影响因子：
9.7
通讯作者：
Redfield, Margaret M.
中科院分区：
文献类型：
--
作者：
Chaanine, Antoine H.;Joyce, Lyle D.;Redfield, Margaret M.
背景：FOXO3a（叉头箱O3a）-BNIP3 （b细胞淋巴瘤2/腺病毒E1B 19kDa相互作用蛋白3）通路调节线粒体动力学和功能，并参与心力衰竭啮齿动物模型的心肌重构。我们试图研究这一途径的表达以及线粒体生物发生（PGC-1a[过氧化物酶体增殖物激活受体-]）的表达。coactivator1 -1a])、动力学（DRP-1[动力蛋白相关蛋白1]、OPA-1[视神经萎缩1]和MFN 2[丝裂酶2]）、氧化磷酸化（柠檬酸合成酶和电子传递链复合物）标志物和COX IV（细胞色素C氧化酶）活性在瓣瓣性或缺血性心脏病和心力衰竭伴射血分数保留（HFpEF）或心力衰竭伴射血分数降低（HFrEF）患者的心肌中。方法和结果：在主动脉瓣置换术(HFpEF(AVR), n=5，心包下左心室活检（10x1x1 mm3）；HFrEFAVR, n=4)，冠状动脉旁路移植术(HFpEF(CABG), n=5；HFrEFCABG, n=5)或左心室辅助装置植入（HFrEFLVAD, n=4）。来自左心室功能正常患者（n=2）和来自供体心脏（n=3）的心外膜下活检作为对照组（正常）。与正常人相比，HFpEF组线粒体碎裂、嵴破坏明显，线粒体面积减小；1.00 +/- 0.09 vs 0.71 +/- 0.08；P = 0.016。这些线粒体形态变化在HFrEF组更为明显（0.54 +/- 0.06）；P=0.002 HFpEF vs . HFrEF。BNIP3（单体+二聚体）在HFpEF（3.99 +/- 2.44）和HFrEF（5.19 +/- 1.70）中的表达较正常增高；P=0.004
BACKGROUND: The FOXO3a (forkhead box O3a)-BNIP3 (B-cell lymphoma 2/adenovirus E1B 19kDa interacting protein 3) pathway modulates mitochondrial dynamics and function and contributes to myocardial remodeling in rodent models of heart failure. We sought to investigate the expression of this pathway along with the expression of mitochondrial biogenesis (PGC-1a [peroxisome proliferator-activated receptor-. coactivator-1a]), dynamics (DRP-1 [dynamin-related protein 1], OPA-1 [optic atrophy 1], and MFN 2 [mitofusin 2]), and oxidative phosphorylation (citrate synthase and electron transport chain complexes) markers and COX IV (cytochrome C oxidase) activity in myocardium from patients with valvular or ischemic heart disease and heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF).METHODS AND RESULTS: Subepicardial left ventricular biopsies (10x1x1 mm3) were obtained at aortic valve replacement (HFpEF(AVR), n=5; and HFrEFAVR, n=4), coronary artery bypass grafting (HFpEF(CABG), n=5; and HFrEFCABG, n=5), or left ventricular assist device implantation (HFrEFLVAD, n=4). Subepicardial biopsies from patients with normal left ventricular function (n=2) and from donor hearts (n=3) served as controls (normal). Relative to normal, mitochondrial fragmentation and cristae destruction were evident, and mitochondrial area was decreased in HFpEF; 1.00 +/- 0.09 versus 0.71 +/- 0.08; P=0.016. These mitochondrial morphological changes were more pronounced in HFrEF (0.54 +/- 0.06); P=0.002 HFpEF versus HFrEF. BNIP3 (monomer+ dimer) expression was increased in HFpEF (3.99 +/- 2.44) and in HFrEF (5.19 +/- 1.70) relative to normal; P=0.004 and P