Time course label-free quantitative analysis of cardiac muscles of rats after myocardial infarction
Time course label-free quantitative analysis of cardiac muscles of rats after myocardial infarction
复制标题
心肌梗死后大鼠心肌时程无标记定量分析
DOI：
10.1039/c3mb70422j
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Wang, Wei
中科院分区：
文献类型：
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作者：
Li, Chun;Qiu, Qi;Wang, Wei
心力衰竭是世界范围内死亡率和发病率的主要原因，也是多种复杂疾病的最终结局。这反映了我们对其潜在分子机制的不完全理解，并进一步增加了疾病的复杂性。为了更好地了解心衰的分子机制，我们研究了心肌梗死大鼠与假手术组大鼠在术后第4、14、28、45天心脏组织动态蛋白质组学差异。采用基于纳米级超高效液相色谱- esi - mse的无标记定量蛋白质组学方法，在8组的4个时间点鉴定了133个蛋白质。急性心肌梗死（AMI）后大鼠左室（LV）组织中13种非冗余蛋白发生动态变化，包括细胞骨架蛋白、代谢酶、氧化应激相关蛋白和离子通道蛋白。网络分析表明，该差异蛋白可能在脂质代谢和肥厚性心肌病中起重要作用。western-blot法检测β -actin、α B-crystallin （CryAB）、热休克蛋白8（HSP8）、desmin和l-乳酸脱氢酶B （LDHB）表达的动态变化，结果与无标记定量蛋白质组学结果一致。相关分析表明，CryAB和desmin与心功能（射血分数）的线性关系优于心肌肌钙蛋白T （cTNT）。我们的研究结果提供了心肌梗死后蛋白质差异表达的第一个实验证据，使用无时间标记的定量蛋白质组学在体内无缺血再灌注损伤或心肌缺血。这些差异功能蛋白（特别是CryAB和desmin）在心肌梗死期间具有不同的模式，这可能部分解释了心脏康复的潜在机制。
Heart failure is a worldwide cause of mortality and morbidity and is the ultimate ending of a variety of complex diseases. This reflects our incomplete understanding of its underlying molecular mechanisms and furthermore increases the complexity of the disease. To better understand the molecular mechanisms of heart failure, we investigated dynamic proteomic differences between the heart tissue of myocardial infarction rats and the rats in the sham group at days 4, 14, 28, 45 after operation. Using a label-free quantitative proteomic approach based on nanoscale ultra-performance liquid chromatography-ESI-MSE, 133 proteins were identified at the four time points in 8 groups. 13 non-redundant proteins changed dynamically after acute myocardial infarction (AMI) in rat left ventricular (LV) tissue, including cytoskeletal proteins, metabolic enzymes, oxidative stress related proteins and ion channel proteins. The network analysis showed that the differential protein might play an important role in lipid metabolism and hypertrophic cardiomyopathy. The dynamic changes in the expression of beta-actin, alpha B-crystallin (CryAB), heat shock protein 8(HSP8), desmin and L-lactate dehydrogenase B (LDHB) were tested by the western-blot assay, and the results were consistent with the label-free quantitative proteomic results. Correlative analysis indicates that the CryAB and desmin have a better linear relation with heart function (ejection fraction) than cardiac troponin T (cTNT). Our results provide the first experimental evidence of the proteins that are differentially expressed following myocardial infarction, using time-course label-free quantitative proteomics in vivo without ischemia-reperfusion injury or myocardial ischemia. These differential functional proteins (especially CryAB and desmin) have different patterns during the myocardial infarction, which may partially account for the underlying mechanisms involved in cardiac rehabilitation.