Chen Ao, Chen Zhangwei, Xia Yan, Lu Danbo, Jia Jianguo, Hu Kai, Sun Aijun, Zou Yunzeng, Qian Juying, Ge Junbo
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Physiol. 2018 Sep 19;9:1318. doi: 10.3389/fphys.2018.01318. eCollection 2018.
Coronary microembolization (CME) is an important clinical problem, and it is related to poor outcome. The specific molecular mechanisms of CME are not fully understood. In the present study, we established a mice model of CME. Isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technologies identified 249 differentially expressed proteins in the myocardial tissues of CME mice as compared with sham-operated mice. Bioinformatics analysis demonstrated that these differentially expressed proteins were enriched in several energy metabolism or cytoskeleton organization related processes or pathways. Quantitative PCR and Western blotting validation experiments revealed that succinate dehydrogenase (SDHA and SDHB) were upregulated, Rho GDP dissociation inhibitor α (RhoGDIα) and Filamin-A (FLNA) were downregulated significantly in CME mice. These findings indicated that the alternations of the cytoskeleton and energy metabolism pathways play important roles in the pathogenesis of CME, future studies are warranted to verify if targeting these molecules might be useful to alleviate CME injury or not.
冠状动脉微栓塞（CME）是一个重要的临床问题，且与不良预后相关。CME的具体分子机制尚未完全明确。在本研究中，我们建立了CME小鼠模型。采用相对和绝对定量同位素标记（iTRAQ）以及液相色谱-串联质谱（LC-MS/MS）技术，鉴定出与假手术小鼠相比，CME小鼠心肌组织中有249种差异表达蛋白。生物信息学分析表明，这些差异表达蛋白富集于几个与能量代谢或细胞骨架组织相关的过程或通路中。定量PCR和蛋白质免疫印迹验证实验显示，CME小鼠中琥珀酸脱氢酶（SDHA和SDHB）上调，Rho GDP解离抑制剂α（RhoGDIα）和细丝蛋白A（FLNA）显著下调。这些发现表明，细胞骨架和能量代谢途径的改变在CME的发病机制中起重要作用，未来有必要进行研究以验证靶向这些分子是否有助于减轻CME损伤。
