Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models
Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models
复制标题
缺血性和扩张性心肌病小鼠模型的心脏蛋白质组分析
DOI：
10.3389/fphys.2019.00750
复制
发表时间：
2019-06-18
影响因子：
4
通讯作者：
Ge, Junbo
中科院分区：
文献类型：
--
作者：
Lu, Danbo;Xia, Yan;Ge, Junbo
心力衰竭（HF）是一种世界性的流行病，具有不可接受的高发病率和死亡率。了解不同的病理生理机制将有助于HF的预防和个体化治疗。采用心肌梗死（MI）和柯萨奇病毒B3（Coxsackievirus B3）感染的方法分别建立了缺血性心肌病（ICM）和扩张型心肌病（DCM）小鼠模型。同位素标记的相对和绝对定量和液相色谱串联质谱技术被用来确定在控制和失败的心脏蛋白质表达谱。在这项蛋白质组学分析中，共鉴定和比较了1，638种蛋白质。其中286个蛋白质表达差异。通过基因本体论、KEGG通路和独创性通路分析，系统评估差异表达蛋白与生物学功能的潜在联系。与对照组相比，ICM和DCM小鼠心脏差异表达的蛋白质部分相似，主要调控氧化磷酸化、代谢和蛋白质折叠途径。此外，DCM和ICM心肌差异表达的蛋白质在氧化磷酸化、代谢和AMPK信号通路中有明显的调节作用。免疫印迹分析表明SDHB在ICM和DCM心脏中均下调，而UQCRQ、GLUT 4和脂联素在ICM心脏中上调。三磷酸腺苷（ATP）浓度显着降低DCM和ICM心脏。磷酸化AMPK α蛋白表达在DCM组明显降低，而在ICM组明显升高。总之，氧化磷酸化、心脏代谢和蛋白质折叠在HF的发病机制中起关键作用。MI或CVB3感染引起的心力衰竭之间蛋白质表达谱的不同变化证明了HF的异质性。了解蛋白质组谱的差异可以为HF提供更精确的治疗选择。
Heart failure (HF) is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of HF. We established mouse models for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) by inducing myocardial infarction (MI) and Coxsackievirus B3 infection, respectively. Isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry technology was used to identify the protein expression profiles in control and failing hearts. A total of 1,638 proteins were identified and compared in this proteomics analysis. Among them, 286 proteins were differently expressed. Gene ontology, KEGG pathway and ingenuity pathway analysis was performed to systematically assess the potential connections of the differentially expressed proteins to biological functions. Compared with control group, the differentially expressed proteins derived from the hearts of ICM and DCM mice were partially similar and mainly modulated in oxidative phosphorylation, metabolism and protein folding pathways. Moreover, difference still existed, the differentially expressed proteins between DCM and ICM hearts were significantly modulated in oxidative phosphorylation, metabolic and AMPK signaling pathways. Confirmatory western bolt analysis demonstrated that SDHB was down-regulated in both ICM and DCM hearts, while UQCRQ, GLUT4 and adiponectin were up-regulated in ICM hearts. Adenosine triphosphate (ATP) concentration significantly decreased in both DCM and ICM hearts. The protein expression of phospho-AMPKα decreased significantly in DCM hearts, but increased in ICM. In summary, oxidative phosphorylation, cardiac metabolism, and protein folding play critical roles in the pathogenesis of HF. The diverse changes in protein expression profiles between failing hearts induced by either MI or CVB3 infection demonstrated the heterogeneity of HF. Understanding the differences in proteome profiles could offer more precise therapeutic options for HF.