Chatfield Kathryn C, Sparagna Genevieve C, Sucharov Carmen C, Miyamoto Shelley D, Grudis Jonathan E, Sobus Rebecca D, Hijmans Jamie, Stauffer Brian L
Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.
Department of Integrative Physiology, University of Colorado, Boulder, CO, USA.
J Mol Cell Cardiol. 2014 Sep;74:251-9. doi: 10.1016/j.yjmcc.2014.06.002. Epub 2014 Jun 14.
Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is critical for optimal mitochondrial function. CL abnormalities have been demonstrated in the failing rodent and adult human heart. The aim of this study was to determine whether abnormalities in CL content and the CL biosynthesis and remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy (IDC). A cross-sectional analysis of myocardial tissue from 119 IDC and non-failing (NF) control samples was performed. Electrospray ionizing mass spectrometry was used to measure total CL and CL species content in LV tissue. RT-PCR was employed to measure gene expression of the enzymes in the CL biosynthesis and remodeling pathways in both the adult and pediatric heart. Significantly lower total and (18:2)4CL (the beneficial species) content was demonstrated in myocardium from pediatric patients with IDC compared to NF controls. Analysis of mitochondrial gene transcripts was used to demonstrate that there is no decrease in mitochondrial content. Expression of two biosynthesis enzymes and one remodeling enzyme was significantly lower in pediatric IDC compared to NF controls. Expression of two phospholipases involved in CL degradation were also altered, one up- and one down-regulated. Except for one remodeling enzyme, these changes are unique from those in the failing adult heart. Similar to what has been seen in adults and in a rat model of IDC, total and (18:2)4CL are lower in pediatric IDC. Unique CL species profiles are seen in heart tissue from children with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme expression likely explain the differences in CL profiles observed in IDC and implicate unique age-related mechanisms of disease.
心磷脂是线粒体内膜中一种独特的磷脂，对线粒体的最佳功能至关重要。在衰竭的啮齿动物和成年人心脏中已证实存在心磷脂异常。本研究的目的是确定小儿特发性扩张型心肌病（IDC）中是否存在心磷脂含量以及心磷脂生物合成和重塑途径的异常。对119例IDC和非衰竭（NF）对照样本的心肌组织进行了横断面分析。采用电喷雾电离质谱法测量左心室组织中的总心磷脂和心磷脂种类含量。采用逆转录聚合酶链反应（RT-PCR）测量成人和小儿心脏中心磷脂生物合成和重塑途径中酶的基因表达。与NF对照组相比，小儿IDC患者心肌中的总心磷脂和（18:2）4心磷脂（有益种类）含量显著降低。线粒体基因转录本分析表明线粒体含量没有减少。与NF对照组相比，小儿IDC中两种生物合成酶和一种重塑酶的表达显著降低。参与心磷脂降解的两种磷脂酶的表达也发生了改变，一种上调，一种下调。除了一种重塑酶外，这些变化与衰竭的成年心脏中的变化不同。与在成人和IDC大鼠模型中观察到的情况类似，小儿IDC中的总心磷脂和（18:2）4心磷脂含量较低。与成人相比，小儿IDC心脏组织中的心磷脂种类谱独特。心磷脂生物合成和重塑酶表达的差异可能解释了在IDC中观察到的心磷脂谱差异，并暗示了与年龄相关的独特疾病机制。
