Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling
Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling
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DOI：
10.1152/ajpheart.00945.2015
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发表时间：
2016-11-01
影响因子：
4.8
通讯作者：
Driesen, Ronald B.
中科院分区：
文献类型：
--
作者：
Galan, Diogo T.;Bito, Virginie;Driesen, Ronald B.
心肌梗死（MI）后左心室（LV）的瘢痕形成和重塑导致收缩功能降低的缺血性心肌病。可能存在与持续缺血相关的区域差异。我们研究了线粒体功能和结构在心肌梗死邻近心肌灌注减少（MI邻近）和较少，所以在远程，非缺血心肌（MI远程）的假设。我们使用慢性冠状动脉狭窄和MI的猪模型（n = 13）。与假手术动物相比，干预后6周的功能和灌注MR成像显示射血分数降低和整体室壁应力增加（Sham; n = 14）。与假手术组相比，MI邻近组的局部应变减少，收缩储备减少; MI远程组的应变也减少，但对多巴酚丁胺有反应，灌注正常。毛细血管密度不变。从这两个地区分离的心肌细胞降低了基础和最大耗氧率，以及通过复合物I和II，但复合物IV活性不变。呼吸减少与线粒体密度的可检测减少无关。AMPK或葡萄糖转运蛋白表达水平无显著变化，但糖原含量在MI邻近和MI远程均显著增加。糖原的积累主要是核周的线粒体在这方面较小，但只有在MI相邻的地方也subsarcolemmal线粒体较小。总之，心肌梗死后，所有LV区域均发生线粒体呼吸减少和糖原蓄积，表明灌注减少不会导致额外的特定变化，血流动力学负荷增加是线粒体功能变化的主要驱动因素。
Scarring and remodeling of the left ventricle (LV) after myocardial infarction (MI) results in ischemic cardiomyopathy with reduced contractile function. Regional differences related to persisting ischemia may exist. We investigated the hypothesis that mitochondrial function and structure is altered in the myocardium adjacent to MI with reduced perfusion (MIadjacent) and less so in the remote, nonischemic myocardium (MIremote). We used a pig model of chronic coronary stenosis and MI (n = 13). Functional and perfusion MR imaging 6 wk after intervention showed reduced ejection fraction and increased global wall stress compared with sham-operated animals (Sham; n = 14). Regional strain in MIadjacent was reduced with reduced contractile reserve; in MIremote strain was also reduced but responsive to dobutamine and perfusion was normal compared with Sham. Capillary density was unchanged. Cardiac myocytes isolated from both regions had reduced basal and maximal oxygen consumption rate, as well as through complex I and II, but complex IV activity was unchanged. Reduced respiration was not associated with detectable reduction of mitochondrial density. There was no significant change in AMPK or glucose transporter expression levels, but glycogen content was significantly increased in both MIadjacent and MIremote. Glycogen accumulation was predominantly perinuclear; mitochondria in this area were smaller but only in MIadjacent where also subsarcolemmal mitochondria were smaller. In conclusion, after MI reduction of mitochondrial respiration and glycogen accumulation occur in all LV regions suggesting that reduced perfusion does not lead to additional specific changes and that increased hemodynamic load is the major driver for changes in mitochondrial function.