Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics.
Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics.
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严重缺血性心肌病患者心外膜脂肪组织细胞外基质重塑异常：比较定量蛋白质组学的见解
DOI：
10.1038/srep43787
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发表时间：
2017-03-03
影响因子：
4.6
通讯作者：
Wei X
中科院分区：
文献类型：
--
作者：
Jiang DS;Zeng HL;Li R;Huo B;Su YS;Fang J;Yang Q;Liu LG;Hu M;Cheng C;Zhu XH;Yi X;Wei X
大量证据表明，心外膜脂肪组织(EAT)的体积和厚度与冠状动脉疾病(CAD)呈正相关。然而，人类心肌缺血后EAT的确切病理变化在很大程度上仍不清楚。在目前的研究中，我们应用比较定量蛋白质组学来阐明缺血性心肌病(ICM)患者的EAT改变的生物学过程。本研究共成功地对1649个蛋白质进行了定量，其中165个蛋白质在ICM个体的EAT中发生了显著的变化(在两次重复中的比值为<；0.8或>；1.2倍，p<； 为0.05)。基因本体论(GO)丰富分析表明，在这些调控蛋白中，心脏结构和细胞代谢的表达水平过高。KEGG通路分析显示肥厚型心肌病、心肌细胞内的肾上腺素能信号、细胞外基质(ECM)-受体相互作用、吞噬小体、糖酵解/糖异生以及PPAR信号通路。更重要的是，我们发现ICM患者的EAT中负责细胞外基质组织的蛋白质显著增加。另外，天狼星红(PSR)染色结果显示ICM的胶原纤维含量明显增加，提示ICM患者的EAT经历了细胞外基质重塑，ERK1/2的激活可能是这些病理改变的部分原因。
There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold andp< 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially.